Dietary intake in the Personalized Medicine Research Project: a resource for studies of gene-diet interaction

  • Lacie Strobush1,

    Affiliated with

    • Richard Berg2,

      Affiliated with

      • Deanna Cross1,

        Affiliated with

        • Wendy Foth1,

          Affiliated with

          • Terrie Kitchner1,

            Affiliated with

            • Laura Coleman3 and

              Affiliated with

              • Catherine A McCarty1Email author

                Affiliated with

                Nutrition Journal201110:13

                DOI: 10.1186/1475-2891-10-13

                Received: 12 August 2010

                Accepted: 28 January 2011

                Published: 28 January 2011

                Abstract

                Background

                To describe the dietary intake of participants in the Personalized Medicine Research Project (PMRP), and to quantify differences in nutrient intake by smoking status and APOE4-a genetic marker that has been shown to modify the association between risk factors and outcomes.

                Methods

                The PMRP is a population-based DNA, plasma and serum biobank of more than 20,000 adults aged 18 years and older in central Wisconsin. A questionnaire at enrollment captures demographic information as well as self-reported smoking and alcohol intake. The protocol was amended to include the collection of dietary intake and physical activity via self-reported questionnaires: the National Cancer Institute 124-item Diet History Questionnaire and the Baecke Physical Activity Questionnaire. These questionnaires were mailed out to previously enrolled participants. APOE was genotyped in all subjects.

                Results

                The response rate to the mailed questionnaires was 68.2% for subjects who could still be contacted (alive with known address). Participants ranged in age from 18 to 98 years (mean 54.7) and 61% were female. Dietary intake is variable when comparing gender, age, smoking, and APOE4. Over 50% of females are dietary supplement users; females have higher supplement intake than males, but both have increasing supplement use as age increases. Food energy, total fat, cholesterol, protein, and alcohol intake decreases as both males and females age. Female smokers had higher macronutrient intake, whereas male nonsmokers had higher macronutrient intake. Nonsmokers in both genders use more supplements. In females, nonsmokers and smokers with APOE4 had higher supplement use. In males, nonsmokers with APOE4 had higher supplement use between ages 18-39 only, and lower supplement use at ages above 39. Male smokers with APOE4 had lower supplement use.

                Conclusion

                Dietary intake in PMRP subjects is relatively consistent with data from the National Health and Nutrition Examination Survey (NHANES). Findings suggest a possible correlation between the use of supplements and APOE4. The PMRP dietary data can benefit studies of gene-environment interactions and the development of common diseases.

                Background

                With the completion of the Human Genome Project, the laboratory tools to quantify genetic variation in human populations exist. Analyzing genetic variation could lead to the discovery of genetic predictors of disease. In addition to those predictors, it is important to quantify gene-environment interactions that modify genetic associations. Dietary intake is associated with multiple health outcomes and is one of the critical, potentially modifiable, environmental exposures to consider in gene-environment studies [1]. Food frequency questionnaires (FFQ) are the most cost-effective tool to measure usual dietary intake in large cohort studies, but caution must be taken with the interpretation and use of macronutrient data from FFQ [1]. Interactions involving alcohol intake as an environmental factor have been studied to illustrate its impact on development of certain health outcomes [2]. Another common, modifiable, environmental risk factor for consideration in gene-environment studies is smoking; dietary intake has been shown to vary by smoking status [3].

                Apolipoprotein E (APOE) is one of the most commonly researched genes in studies of gene-environment interactions. Through its function as a ligand and its involvement with chylomicrons, very-low density lipoproteins (VLDL), and high-density lipoproteins (HDLs), APOE helps maintain cholesterol and fat levels in the body [4]. The APOE gene has three alleles, one of which is E4. The E4 allele has been associated with both coronary heart disease (CHD) and early onset of Alzheimer's disease [5]. Total cholesterol and LDL cholesterol levels in general are highest in people who have an E4 allele [6, 7]. Some studies have suggested that APOE4 carriers who are smokers are at increased risk for coronary heart disease compared to non-smokers [5].

                The Personalized Medicine Research Project (PMRP) is a population-based DNA, plasma and serum biobank designed to facilitate genetic epidemiology and pharmacogenetic studies [811]. The comprehensive medical record of the Marshfield Clinic is ideal for the identification of affected cases and appropriate controls; however, limited information about personal exposure is collected in a standardized fashion in the context of routine clinical care. Therefore, assessments of known, potentially modifiable, risk factors for disease were included in the study protocol. They include smoking status, alcohol intake, and a detailed FFQ and physical activity questionnaire. The purpose of this paper is to describe the PMRP biobank as a resource for gene-diet studies, to quantify the extent to which smoking status, alcohol consumption, and the APOE genotype are associated with dietary intake in the population, and to explain how these factors may need to be considered as co-variants in future gene-nutrient studies.

                Methods

                Personalized Medicine Research Project (PMRP)

                Details of the PMRP have been published previously [811]. In summary, the project was designed to establish a large biobank consisting of DNA, plasma and serum from a large representative sample. Since central Wisconsin has a relatively stable population and the majority of residents receive care at a Marshfield Clinic, the geographic area is ideal for research over a long period of time. Participants that were invited were residents of at least 18 years of age, living in one of 19 zip-codes surrounding Marshfield, WI, and the vast majority received most of their medical care in the Marshfield Clinic system. After subjects have signed the written consent form, which allows access to their comprehensive Marshfield Clinic medical record, subjects complete a brief questionnaire about demographics, smoking status, alcohol intake, and health history. DNA, plasma, and serum samples were extracted and stored from whole blood. To extract the DNA, the Gentra's AUTOPURE® system was used. White blood cells were isolated and lysed; through multiple steps of centrifugation and decanting, DNA was obtained, washed and stored at -80°C [8]. All procedures were reviewed and approved by the Marshfield Clinic Institutional Review Board.

                Quantification of dietary intake

                The study protocol was amended after nearly 18,000 subjects were enrolled in PMRP to include usual dietary intake and physical activity. Usual dietary intake was measured using the validated National Cancer Institute 124-item Diet History Questionnaire (DHQ) [1217]. For those subjects already enrolled, the DHQ was mailed out, with a second mailing and follow-up phone calls as needed to increase the participation rate. The completed questionnaires were scanned and nutrient files were created using the software package Diet*Calc (http://​riskfactor.​cancer.​gov/​DHQ/​dietcalc/​). Questionnaires with more than half of the pages or items not complete were excluded from analysis. Standard units were used. ATE CSFII refers to the units for vitamin E. CSFII stands for Continuing Survey of Food Intakes by Individuals; ATE stands for alpha-tocopherol equivalent, which is a form of vitamin E absorbed by humans. IU and RE refer to the units for measuring vitamin A. IU stands for international units, and RE stands for retinol equivalents.

                Quantification of APOE4 genotype

                Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry was used to genotype the polymorphisms of the APOE gene. PCR reactions, which used primers designed by the Assay Designer 2.05-software from Sequenom, amplified designated regions of DNA. Primer extension reactions were performed to generate allele-specific products that are one base longer than the original primer. The products were placed onto a matrix arrayed silicon chip and analyzed by a MALDI-TOF mass spectrometer and Sequenom SpectroTYPER 3.4 software. The mass spectrometer determines alleles based on different molecular weights [11].

                Statistical analyses

                Preliminary analyses included tabular and graphical summaries describing participant demographics, dietary intake, and APOE genotypes. In the primary study analyses we analyze dietary intake for associations with body size (BMI), smoking status and APOE4, while controlling for expected age and gender differences. Stratification and graphical displays were used to investigate the plausibility and consistency of potential associations, and to identify potential interactions and confounding. Group comparisons of dietary intake stratified by gender and age were conducted using rank-based methods (Wilcoxon and Kruskal-Wallis tests). Analyses were conducted using SAS® (version 9.2, SAS Inc., Cary, NC). Results were considered statistically significant at the 5% level (p < 0.05) without adjustment for multiple comparisons.

                Results

                The response rate to the mailed questionnaires was 62.8% for subjects who could still be contacted (alive with known address). Approximately 3% of participants could not be located and 4% were deceased. Figure 1 illustrates the tracking of questionnaires mailed out to participants. The 11,166 with dietary information ranged in age from 18 to 98 years (mean 54.9 years) and 6821 (61%) were female. Demographic characteristics of the dietary cohort and a comparison with non-responders are summarized in Table 1. Responders were more likely to be female, older, and never smokers.
                http://static-content.springer.com/image/art%3A10.1186%2F1475-2891-10-13/MediaObjects/12937_2010_337_Fig1_HTML.jpg
                Figure 1

                Diagram of DHQ mailing for PMRP dietary cohort as of September 16, 2009. The diagram includes participants enrolled on or before 2/3/09. *nursing home and non-English speaking, **too many missing fields on the DHQ

                Table 1

                Descriptive characteristics of the dietary cohort and comparison with non-responders

                 

                Males

                Females

                Overall

                Non-responders

                Subjects (n %)

                4,345 39%

                6,821 61%

                11,166

                8,413 52% Female

                Median age (yr)

                57.1

                53.4

                54.9

                46.4

                   Minimum

                18

                18

                18

                18

                   Maximum

                96

                98

                98

                103

                Diabetes (n %)

                769 18%

                904 13%

                1673 15%

                1250 15%

                Smoking history (n %)

                    

                Never

                2024 47%

                4211 62%

                6235 56%

                4298 51%

                Current

                655 15%

                983 14%

                1638 15%

                2065 25%

                Other or unknown

                1666 38%

                1627 24%

                3293 29%

                2050 24%

                E4 genotype (n %)

                1198 28%

                1750 26%

                2948 26%

                2271 27%

                Median BMI (kg/m2)

                28.7

                27.8

                28.2

                27.8

                Minimum

                14.7

                15.0

                14.7

                14.9

                Maximum

                71.1

                69.9

                71.1

                66.4

                Median HDL (mg/dL)

                43.0

                53.5

                49.0

                46.0

                Minimum

                16.0

                15.0

                15.0

                11.0

                Maximum

                135.0

                147.0

                147.0

                141.0

                Dietary intake varied by age, gender, smoking and the E4 allele. Trends seen within data are statistically significant, unless otherwise noted. Table 2 compares the percent use of various supplements between females and males of different age groups. The percent use of supplements for females increases as age group increases. Over fifty percent of women in each age group consume supplements; similar trends are seen for males. When comparing males and females in the same age group, the percent-use of the various supplements is lower in males than in females. Vitamin C supplements are consumed most frequently by both females and males.
                Table 2

                Percent use of supplements by gender and age in the Personalized Medicine Research Project

                Females

                   

                Males

                   

                Age Group

                18-39

                40-59

                60+

                Age Group

                18-39

                40-59

                60+

                N*

                1644

                2645

                2512

                N*

                824

                1620

                1900

                 

                % use

                % use

                % use

                 

                % use

                % use

                % use

                Vit. A IU

                59.6

                65.1

                71.2

                Vit. A IU

                38.3

                47.3

                56.6

                Vit. A RAE

                59.6

                65.1

                71.2

                Vit. A RAE

                38.3

                47.3

                56.6

                Beta Car.

                59.0

                64.7

                70.7

                Beta Car.

                37.9

                47.1

                56.6

                Vit. E

                60.3

                68.9

                75.6

                Vit. E

                38.8

                49.4

                60.4

                Vit. C

                65.2

                72.5

                76.6

                Vit. C

                44.7

                53.4

                62.5

                Thiamin

                59.5

                66.6

                71.6

                Thiamin

                38.0

                47.7

                57.4

                Riboflavin

                59.5

                66.6

                71.6

                Riboflavin

                38.0

                47.7

                57.4

                Niacin

                59.7

                67.0

                72.1

                Niacin

                38.2

                48.3

                58.6

                Vit. B6

                59.8

                67.4

                72.5

                Vit. B6

                38.3

                48.0

                58.3

                Folic Acid

                60.2

                65.3

                71.7

                Folic Acid

                38.1

                47.3

                57.9

                Vit. B12

                58.7

                64.2

                70.0

                Vit. B12

                37.6

                46.7

                56.1

                Calcium

                27.8

                55.0

                69.7

                Calcium

                13.5

                17.3

                30.9

                Magnesium

                54.1

                60.0

                61.1

                Magnesium

                32.9

                42.3

                48.8

                Iron

                56.5

                61.9

                63.4

                Iron

                33.7

                42.7

                50.8

                Zinc

                54.8

                61.2

                62.7

                Zinc

                34.0

                43.3

                50.5

                Copper

                54.1

                60.0

                61.1

                Copper

                32.9

                42.3

                48.8

                Vit. D

                58.7

                64.2

                70.0

                Vit. D

                37.6

                46.7

                56.1

                Selenium

                0.5

                1.6

                2.1

                Selenium

                0.2

                2.2

                5.1

                *N refers to the total number of females or males within the particular age group

                Tables 3 and 4 compare the dietary intake between different age groups of females (Tables 3) and males (Table 4). Supplement-use summaries for the subset who use supplements are listed at the bottom of each table. The results suggest that with increasing age in females, food energy, total fat, cholesterol, protein, and alcohol intake decreases. Conversely, as women age, the average supplement intake increased. Similar trends were observed in males, regarding the mean and median intake of food energy, total fat, cholesterol, protein, alcohol, and supplement intake.
                Table 3

                Dietary intake in females by age in the Personalized Medicine Research Project

                Age Group

                18-39

                40-59

                60+

                 
                 

                N*

                Mean

                Median

                N*

                Mean

                Median

                N*

                Mean

                Median

                K-W Test p-value

                Food energy (kcal)

                2147

                1859.5

                1637.4

                2752

                1674.7

                1522.7

                1997

                1415.5

                1341.1

                < 0.001

                Total fat (g)

                2147

                65.2

                56.1

                2752

                61.6

                53.8

                1997

                51.3

                46.0

                < 0.001

                Cholesterol (mg)

                2147

                199.3

                171.4

                2752

                185.0

                161.7

                1997

                154.3

                137.3

                < 0.001

                Protein (g)

                2147

                71.6

                64.2

                2752

                67.3

                61.7

                1997

                54.5

                50.8

                < 0.001

                Alcohol (g)

                2147

                6.6

                2.1

                2752

                5.9

                1.4

                1997

                3.1

                0.6

                < 0.001

                Vitamin A (IU CSFII)

                2147

                8958.8

                6375.6

                2752

                9921.8

                7354.3

                1997

                8549.4

                6695.0

                < 0.001

                Vitamin A (mcg RE CSFII)

                2147

                1264.8

                1003.5

                2752

                1324.5

                1096.7

                1997

                1157.6

                999.3

                < 0.001

                Vitamin E (mg ATE CSFII)

                2147

                8.3

                6.9

                2752

                8.4

                7.3

                1997

                7.5

                6.6

                < 0.001

                Vitamin C (mg)

                2147

                134.6

                101.3

                2752

                127.1

                104.3

                1997

                124.5

                108.2

                < 0.065

                Zinc (mg)

                2147

                11.0

                9.8

                2752

                10.4

                9.5

                1997

                8.7

                8.1

                < 0.001

                Selenium (mcg)

                2147

                86.2

                76.4

                2752

                81.2

                74.0

                1997

                67.0

                62.1

                < 0.001

                Total Vitamin A Activity (mcg)

                2147

                838.4

                719.7

                2752

                828.2

                719.9

                1997

                721.8

                659.8

                < 0.001

                Beta Carotene

                2147

                3198.6

                2055.7

                2752

                3657.3

                2524.0

                1997

                3101.7

                2276.5

                < 0.001

                Lutein|Zeaxanthin (mcg NDS)

                2147

                2444.7

                1643.3

                2752

                2467.9

                1727.9

                1997

                1998.6

                1474.5

                < 0.001

                Lycopene (mcg NDS R)

                2147

                7726.0

                5611.2

                2752

                6815.3

                4998.7

                1997

                6096.7

                4022.5

                < 0.001

                Beta Carotene Equivalents (mcg)

                2147

                3701.3

                2373.0

                2752

                4237.7

                2899.1

                1997

                3599.2

                2632.4

                < 0.001

                Vitamin E Total

                2147

                7.8

                6.4

                2752

                7.9

                6.7

                1997

                6.7

                5.9

                < 0.001

                Supp. Vitamin A (IU)

                2147

                2094.6

                331.8

                2752

                2928.0

                3571.4

                1997

                3496.9

                5000.0

                < 0.001

                Supp. Vitamin A (mcg RAE)

                2147

                628.4

                99.6

                2752

                878.4

                1071.4

                1997

                1049.1

                1500.0

                < 0.001

                Supp. Beta Carotene

                2147

                246.8

                39.8

                2752

                339.6

                428.6

                1997

                410.7

                600.0

                < 0.001

                Supp. Vitamin E

                2147

                16.8

                4.4

                2752

                58.5

                20.1

                1997

                78.0

                20.1

                < 0.001

                Supp. Vitamin C

                2147

                81.1

                17.1

                2752

                150.7

                60.0

                1997

                176.8

                60.0

                < 0.001

                Supp. Zinc

                2147

                6.1

                1.0

                2752

                8.6

                10.7

                1997

                9.2

                15.0

                < 0.001

                Supp. Selenium

                2147

                0.3

                0.0

                2752

                0.8

                0.0

                1997

                0.8

                0.0

                < 0.001

                Supplement Users Only

                          

                Supp. Vitamin A (IU)

                992

                3497.2

                5000.0

                1722

                4182.1

                5000.0

                1789

                4843.7

                5000.0

                < 0.001

                Supp. Vitamin A (mcg RAE)

                992

                1049.2

                1500.0

                1722

                1254.6

                1500.0

                1789

                1453.1

                1500.0

                < 0.001

                Supp. Beta Carotene

                982

                410.2

                600.0

                1712

                492.9

                600.0

                1775

                572.1

                600.0

                < 0.001

                Supp. Vitamin E

                1003

                24.6

                20.1

                1823

                74.1

                20.1

                1900

                100.0

                20.1

                < 0.001

                Supp. Vitamin C

                1085

                115.5

                60.0

                1917

                188.4

                60.0

                1924

                229.1

                60.0

                < 0.001

                Supp. Zinc (mg)

                900

                1.4

                2.0

                1587

                1.6

                2.0

                1535

                1.8

                2.0

                < 0.001

                Supp. Selenium (mcg)

                9

                42.9

                42.9

                43

                42.9

                42.9

                53

                42.9

                42.9

                1.000

                *N refers to the total number of participants per age group

                Table 4

                Dietary intake in males by age in the Personalized Medicine Research Project

                Age Group

                18-39

                  

                40-59

                  

                60+

                   
                 

                N*

                Mean

                Median

                N*

                Mean

                Median

                N*

                Mean

                Median

                K-W Test p-value

                Total fat (g)

                1105

                99.2

                85.9

                1764

                87.0

                74.7

                1515

                69.6

                61.9

                < 0.001

                Cholesterol (mg)

                1105

                304.0

                258.1

                1764

                263.1

                226.1

                1515

                214.9

                186.8

                < 0.001

                Protein (g)

                1105

                106.0

                91.1

                1764

                91.7

                81.3

                1515

                71.2

                64.4

                < 0.001

                Alcohol (g)

                1105

                21.4

                5.1

                1764

                15.5

                3.5

                1515

                10.2

                1.8

                < 0.001

                Vitamin A (IU CSFII)

                1105

                9292.7

                6715.6

                1764

                9490.8

                7456.3

                1515

                8731.1

                6842.3

                < 0.001

                Vitamin A (mcg RE CSFII)

                1105

                1442.2

                1152.8

                1764

                1384.7

                1201.5

                1515

                1270.6

                1086.9

                < 0.001

                Vitamin E (mg ATE CSFII)

                1105

                10.9

                8.8

                1764

                10.2

                8.7

                1515

                9.0

                7.8

                < 0.001

                Vitamin C (mg)

                1105

                157.3

                113.0

                1764

                137.4

                111.4

                1515

                125.8

                107.5

                < 0.034

                Zinc (mg)

                1105

                16.3

                14.0

                1764

                14.3

                12.6

                1515

                11.6

                10.3

                < 0.001

                Selenium (mcg)

                1105

                130.9

                114.0

                1764

                116.1

                102.4

                1515

                92.1

                83.5

                < 0.001

                Total Vitamin A Activity (mcg)

                1105

                1048.6

                862.2

                1764

                944.1

                838.1

                1515

                848.5

                733.7

                < 0.001

                Beta Carotene

                1105

                3111.2

                1971.9

                1764

                3290.3

                2335.0

                1515

                3035.9

                2195.7

                < 0.001

                Lutein|Zeaxanthin (mcg NDS)

                1105

                2640.6

                1740.4

                1764

                2368.8

                1773.8

                1515

                2140.5

                1544.8

                < 0.001

                Lycopene (mcg NDS R)

                1105

                10491

                7941.1

                1764

                9438.5

                6621.3

                1515

                7770.7

                5163.8

                < 0.001

                Beta Carotene Equivalents (mcg)

                1105

                3571.6

                2266.4

                1764

                3818.0

                2697.1

                1515

                3521.6

                2538.3

                < 0.001

                Vitamin E Total

                1105

                10.0

                8.1

                1764

                9.3

                8.0

                1515

                7.9

                6.8

                < 0.001

                Supp. Vitamin A (IU)

                1105

                1222.9

                0.0

                1764

                2258.9

                82.1

                1515

                2806.4

                3571.4

                < 0.001

                Supp. Vitamin A (mcg RAE)

                1105

                366.9

                0.0

                1764

                677.7

                24.6

                1515

                841.9

                1071.4

                < 0.001

                Supp. Beta Carotene

                1105

                144.1

                0.0

                1764

                264.9

                9.9

                1515

                327.5

                428.6

                < 0.001

                Supp. Vitamin E

                1105

                11.6

                0.0

                1764

                35.9

                2.4

                1515

                50.5

                20.1

                < 0.001

                Supp. Vitamin C

                1105

                54.8

                0.0

                1764

                106.3

                17.1

                1515

                130.8

                60.0

                < 0.001

                Supp. Zinc

                1105

                3.8

                0.0

                1764

                6.6

                0.0

                1515

                7.8

                0.0

                < 0.001

                Supp. Selenium

                1105

                0.2

                0.0

                1764

                1.2

                0.0

                1515

                2.2

                0.0

                < 0.001

                Supplement Users Only

                          

                Supp. Vitamin A (IU)

                316

                3059.8

                3571.4

                766

                4229.3

                5000.0

                1075

                4930.3

                5000.0

                < 0.001

                Supp. Vitamin A (mcg RAE)

                316

                917.9

                1071.4

                766

                1268.8

                1500.0

                1075

                1479.1

                1500.0

                < 0.001

                Supp. Beta Carotene

                312

                360.5

                428.6

                763

                494.1

                600.0

                1076

                579.4

                600.0

                < 0.001

                Supp. Vitamin E

                320

                22.9

                14.4

                801

                61.6

                20.1

                1147

                83.4

                20.1

                < 0.001

                Supp. Vitamin C

                368

                115.6

                60.0

                865

                173.2

                60.0

                1187

                212.1

                60.0

                < 0.001

                Supp. Zinc (mg)

                271

                1.2

                1.4

                685

                1.6

                2.0

                927

                1.9

                2.0

                < 0.001

                Supp. Selenium (mcg)

                2

                42.9

                42.9

                36

                42.9

                42.9

                96

                42.9

                42.9

                1.000

                *N refers to the total number of participants per age group

                Tables 5, 6 and 7 illustrate supplement use stratified by age group, gender, smoking, and E4 allele status. Comparing females on smoking status alone, the nonsmokers generally consume more dietary supplements throughout all age groups. This similar trend is seen in males as well. The data show, once again, that females had more supplement use percentages than males when comparing relative age groups. Differences in supplement use are seen between those that have the E4 allele and those that do not. In the nonsmoking females, those with the E4 allele had higher supplement intake than nonsmokers without E4. Current smoking females with E4 have a higher supplement intake than those without E4. This trend is relatively consistent throughout all age groups in females. The data show some inconsistencies between males and females. In nonsmoking males between ages 18-39, those with E4 have higher percent use than those without E4; in the same age group, smokers without the E4 allele had higher use of supplements. In the other two age groups, nonsmoking males with E4 have lower percent use of supplements than those without E4. Current smoking males with E4 had a lower percent use than those without E4. This trend is seen in current smokers among each age group in males. Supplement use by E4 differed between genders. In general, females with E4 had higher supplement use percentages, and males with E4 had lower supplement use percentages compared to those without E4.
                Table 5

                Percent use of supplements by gender, smoking status, and E4 in subjects aged 18-39 in the Personalized Medicine Research Project

                 

                Never Smoked

                Current Smokers

                 

                With E4

                No E4

                With E4

                No E4

                Females

                    

                N*

                293

                775

                104

                296

                 

                % Use

                % Use

                % Use

                % Use

                Vit. A IU

                68.9

                61.4

                49.0

                48.0

                Vit. A RAE

                68.9

                61.4

                49.0

                48.0

                Beta Car.

                68.3

                60.5

                49.0

                48.3

                Vit. E

                69.6

                61.9

                51.0

                49.0

                Vit. C

                73.0

                66.7

                52.9

                53.7

                Thiamin

                68.3

                60.9

                49.0

                48.6

                Riboflavin

                68.3

                60.9

                49.0

                48.6

                Niacin

                68.3

                61.4

                49.0

                48.6

                Vit. B6

                68.3

                61.4

                49.0

                49.0

                Folic Acid

                67.9

                62.1

                50.0

                49.0

                Vit. B12

                67.9

                60.1

                48.1

                48.0

                Calcium

                32.4

                25.0

                27.9

                25.0

                Magnesium

                62.1

                55.4

                44.2

                44.9

                Iron

                63.1

                57.5

                45.2

                49.0

                Zinc

                63.1

                56.0

                45.2

                45.6

                Copper

                62.1

                55.4

                44.2

                44.9

                Vit. D

                67.9

                60.1

                48.1

                48.0

                Selenium

                0.0

                1.0

                0.0

                0.3

                Males

                    

                N*

                125

                377

                59

                156

                 

                % Use

                % Use

                % Use

                % Use

                Vit. A IU

                40.8

                39.5

                30.5

                35.9

                Vit. A RAE

                40.8

                39.5

                30.5

                35.9

                Beta Car.

                42.4

                38.7

                28.8

                35.3

                Vit. E

                40.8

                39.5

                33.9

                37.2

                Vit. C

                46.4

                43.8

                40.7

                46.8

                Thiamin

                40.8

                38.7

                30.5

                35.9

                Riboflavin

                40.8

                38.7

                30.5

                35.9

                Niacin

                41.6

                38.7

                32.2

                35.9

                Vit. B6

                40.8

                38.7

                32.2

                36.5

                Folic Acid

                40.8

                38.7

                32.2

                35.9

                Vit. B12

                40.8

                38.7

                28.8

                35.3

                Calcium

                16.0

                11.9

                15.3

                12.8

                Magnesium

                34.4

                33.7

                25.4

                30.8

                Iron

                34.4

                33.7

                30.5

                33.3

                Zinc

                35.2

                34.7

                30.5

                31.4

                Copper

                34.4

                33.7

                25.4

                30.8

                Vit. D

                40.8

                38.7

                28.8

                35.3

                Selenium

                0.0

                0.30

                1.70

                0.0

                *N refers to the number of participants

                Table 6

                Percent use of supplements by gender, smoking status, and E4 in subjects aged 40-59 in the Personalized Medicine Research Project

                 

                Never Smoked

                Current Smokers

                 

                With E4

                No E4

                With E4

                No E4

                Females

                    

                N*

                426

                1186

                105

                306

                 

                % Use

                % Use

                % Use

                % Use

                Vit. A IU

                70.9

                64.3

                65.7

                57.8

                Vit. A RAE

                70.9

                64.3

                65.7

                57.8

                Beta Car.

                70.4

                63.8

                65.7

                56.9

                Vit. E

                74.2

                68.0

                65.7

                61.1

                Vit. C

                78.4

                72.2

                71.4

                64.1

                Thiamin

                73.5

                65.5

                67.6

                58.5

                Riboflavin

                73.5

                65.5

                67.6

                58.5

                Niacin

                73.9

                65.9

                67.6

                58.5

                Vit. B6

                73.5

                66.6

                69.5

                59.5

                Folic Acid

                71.4

                64.6

                67.6

                57.5

                Vit. B12

                70.2

                63.4

                65.7

                56.9

                Calcium

                59.9

                55.6

                42.9

                43.8

                Magnesium

                67.1

                58.9

                56.2

                53.6

                Iron

                68.3

                61.4

                57.1

                54.9

                Zinc

                67.8

                59.9

                57.1

                54.2

                Copper

                67.1

                58.9

                56.2

                53.6

                Vit. D

                70.2

                63.4

                65.7

                56.9

                Selenium

                1.9

                1.5

                1.9

                1.0

                Males

                    

                N*

                230

                624

                91

                215

                 

                % Use

                % Use

                % Use

                % Use

                Vit. A IU

                46.1

                47.1

                41.8

                46.0

                Vit. A RAE

                46.1

                47.1

                41.8

                46.0

                Beta Car.

                46.1

                47.1

                38.5

                46.5

                Vit. E

                47.8

                49.5

                40.7

                47.4

                Vit. C

                50.9

                53.0

                49.5

                51.6

                Thiamin

                45.7

                47.6

                38.5

                47.0

                Riboflavin

                45.7

                47.6

                38.5

                47.0

                Niacin

                45.7

                48.2

                38.5

                47.9

                Vit. B6

                46.5

                47.6

                39.6

                47.0

                Folic Acid

                46.5

                47.1

                38.5

                46.5

                Vit. B12

                45.7

                46.8

                37.4

                46.0

                Calcium

                10.4

                17.8

                13.2

                15.3

                Magnesium

                43.0

                41.5

                33.0

                41.9

                Iron

                43.0

                42.0

                34.1

                41.9

                Zinc

                43.9

                42.1

                35.2

                42.8

                Copper

                43.0

                41.5

                33.0

                41.9

                Vit. D

                45.7

                46.8

                37.4

                46.0

                Selenium

                2.2

                1.4

                2.2

                2.8

                *N refers to the number of participants

                Table 7

                Percent use of supplements by gender, smoking status, and E4 in subjects aged 60 and older in the Personalized Medicine Research Project

                 

                Never Smoked

                Current Smokers

                 

                With E4

                No E4

                With E4

                No E4

                Females

                    

                N*

                374

                1157

                39

                133

                 

                % Use

                % Use

                % Use

                % Use

                Vit. A IU

                73.3

                71.3

                71.8

                60.9

                Vit. A RAE

                73.3

                71.3

                71.8

                60.9

                Beta Car.

                72.7

                70.7

                71.8

                61.7

                Vit. E

                78.3

                76.2

                74.4

                66.9

                Vit. C

                79.9

                76.1

                74.4

                72.2

                Thiamin

                74.3

                71.6

                71.8

                61.7

                Riboflavin

                74.3

                71.6

                71.8

                61.7

                Niacin

                74.3

                72.4

                71.8

                61.7

                Vit. B6

                74.9

                72.5

                71.8

                62.4

                Folic Acid

                74.1

                71.3

                71.8

                63.9

                Vit. B12

                72.5

                69.8

                71.8

                60.2

                Calcium

                68.2

                72.0

                56.4

                58.6

                Magnesium

                64.2

                60.3

                64.1

                51.1

                Iron

                65.8

                62.9

                64.1

                54.1

                Zinc

                65.0

                62.1

                66.7

                51.9

                Copper

                64.2

                60.3

                64.1

                51.1

                Vit. D

                72.5

                69.8

                71.8

                60.2

                Selenium

                1.6

                2.0

                0.0

                3.8

                Males

                    

                N*

                190

                477

                33

                101

                 

                % Use

                % Use

                % Use

                % Use

                Vit. A IU

                47.9

                57.9

                39.4

                56.4

                Vit. A RAE

                47.9

                57.9

                39.4

                56.4

                Beta Car.

                47.9

                58.1

                39.4

                57.4

                Vit. E

                53.7

                60.6

                45.5

                57.4

                Vit. C

                54.2

                63.5

                48.5

                61.4

                Thiamin

                48.4

                59.5

                39.4

                56.4

                Riboflavin

                48.4

                59.5

                39.4

                56.4

                Niacin

                51.1

                60.4

                39.4

                57.4

                Vit. B6

                48.4

                60.6

                45.5

                57.4

                Folic Acid

                48.4

                58.7

                45.5

                57.4

                Vit. B12

                47.4

                57.2

                39.4

                56.4

                Calcium

                26.8

                32.1

                33.3

                29.7

                Magnesium

                40.5

                50.1

                36.4

                48.5

                Iron

                42.1

                52.4

                36.4

                50.5

                Zinc

                42.1

                52.0

                39.4

                49.5

                Copper

                40.5

                50.1

                36.4

                48.5

                Vit. D

                47.4

                57.2

                39.4

                56.4

                Selenium

                4.7

                6.5

                3.0

                1.0

                *N refers to the number of participants

                Table 8 compares the dietary intake between smoking and nonsmoking females and males. For females, the data suggest that the dietary intake for food energy, total fat, cholesterol, alcohol, vitamin E (mg ATE CSFII), selenium, and lycopene was higher in smokers versus nonsmokers. Furthermore, the dietary intake for vitamin A (IU CSFII), vitamin A (mcg RE CSFII), and vitamin C was higher in nonsmokers than in smokers. No differences were seen in supplement intake between the two groups. Differences can also be seen between smokers and nonsmokers when comparing 25% and 75% quartile values. The results regarding smoking and dietary intake for males were not statistically significant. Nonsmokers generally consumed healthier diets, as evidenced by using more supplements, consuming higher dietary vitamin C, and consuming less alcohol.
                Table 8

                Dietary intake by gender and smoking status in the Personalized Medicine Research Project. The total number of participants who smoked and never smoked is indicated by "N" beneath the respective category.

                Females

                       
                 

                Never Smoked

                Smoked 100+

                 

                N*

                 

                4262

                 

                2538

                   
                 

                25%

                Median

                75%

                25%

                Median

                75%

                Wilcoxon p-value

                Food energy (kcal)

                1092.3

                1468.8

                1942.1

                1146.3

                1539.9

                2066.2

                < 0.001

                Total fat (g)

                35.7

                51.2

                72.3

                37.6

                54.8

                77.2

                < 0.001

                Cholesterol (mg)

                102.8

                153.8

                220.1

                109.6

                164.2

                235.3

                < 0.001

                Protein (g)

                42.4

                58.6

                78.3

                42.9

                60.0

                81.1

                0.056

                Alcohol (g)

                0.1

                1.1

                3.3

                0.3

                1.7

                6.3

                < 0.001

                Vitamin A (IU CSFII)

                4394.1

                6915.6

                11608

                4104.1

                6639.4

                11198

                0.002

                Vitamin A (mcg RE CSFII)

                703.1

                1051.3

                1563.0

                654.6

                1005.5

                1536.2

                0.003

                Vitamin E (mg ATE CSFII)

                4.7

                6.8

                9.9

                4.8

                7.2

                10.5

                0.007

                Vitamin C (mg)

                69.7

                107.1

                158.2

                63.2

                100.4

                157.4

                < 0.001

                Zinc (mg)

                6.6

                9.1

                12.1

                6.6

                9.3

                12.4

                0.089

                Selenium (mcg)

                50.5

                70.2

                94.2

                52.4

                72.9

                99.2

                0.002

                Total Vitamin A Activity (mcg)

                479.9

                706.7

                989.6

                451.1

                692.1

                1000.1

                0.206

                Beta Carotene

                1374.5

                2316.2

                4265.4

                1267.5

                2266.6

                4176.5

                0.060

                Lutein|Zeaxanthin (mcg NDS)

                1029.3

                1636.6

                2579.3

                1002.5

                1615.4

                2619.1

                0.506

                Lycopene (mcg NDS R)

                3026.7

                4815.3

                7901.4

                3194.0

                5075.2

                8470.1

                0.003

                Beta Carotene Equivalents (mcg)

                1586.3

                2689.2

                4912.3

                1468.6

                2609.5

                4793.5

                0.026

                Vitamin E Total

                4.4

                6.3

                9.2

                4.4

                6.5

                9.6

                0.026

                Males

                       
                 

                Never Smoked

                Smoked 100+

                 

                N*

                 

                2045

                  

                2233

                  
                 

                25%

                Median

                75%

                25%

                Median

                75%

                Wilcoxon p-value

                Food energy (kcal)

                1499.7

                2051.0

                2772.5

                1426.6

                1955.4

                2720.8

                0.050

                Total fat (g)

                50.4

                73.9

                104.4

                49.2

                71.2

                104.9

                0.156

                Cholesterol (mg)

                147.1

                222.4

                324.5

                147.5

                216.6

                326.0

                0.685

                Protein (g)

                57.6

                79.3

                110.3

                54.1

                75.5

                105.4

                0.001

                Alcohol (g)

                0.6

                2.8

                10.0

                0.6

                3.5

                15.2

                0.001

                Vitamin A (IU CSFII)

                4734.1

                7164.8

                11634

                4505.0

                6892.0

                10910

                0.054

                Vitamin A (mcg RE CSFII)

                777.6

                1179.8

                1760.9

                744.9

                1109.3

                1652.2

                0.002

                Vitamin E (mg ATE CSFII)

                5.8

                8.4

                12.1

                5.7

                8.3

                12.2

                0.342

                Vitamin C (mg)

                73.1

                113.1

                176.0

                67.8

                107.5

                167.6

                0.004

                Zinc (mg)

                8.9

                12.2

                17.4

                8.5

                11.8

                16.7

                0.006

                Selenium (mcg)

                71.3

                98.8

                136.8

                68.2

                96.8

                134.2

                0.148

                Total Vitamin A Activity (mcg)

                554.6

                834.8

                1209.9

                523.7

                785.4

                1154.5

                0.001

                Beta Carotene

                1294.6

                2163.3

                3954.2

                1333.7

                2184.9

                3822.1

                0.813

                Lutein|Zeaxanthin (mcg NDS)

                1103.4

                1737.5

                2696.4

                1030.2

                1633.7

                2641.8

                0.072

                Lycopene (mcg NDS R)

                3976.0

                6436.8

                10382

                3846.7

                6409.3

                10736

                0.780

                Beta Carotene Equivalents (mcg)

                1499.2

                2499.0

                4593.6

                1528.5

                2523.0

                4431.0

                0.705

                Vitamin E Total

                5.4

                7.6

                11.1

                5.2

                7.5

                11.1

                0.196

                *N refers to the number of participants

                Tables 8 and 9 illustrate the supplement intake between females (Table 9) and males (Table 10) stratified by having the E4 allele or not. The data suggest that females with the E4 allele have higher supplement intake than those without it; however, when looking at the "supplement users only" data, there is little to no difference by E4 status. As for males, the data suggest that those without the E4 allele have higher supplement intake. With some exceptions, the same general trend is seen within the "supplement users only" data.
                Table 9

                Supplement intake by APOE4 genotype in females in the Personalized Medicine Research Project

                 

                With E4

                No E4

                 

                Nutrient

                N*

                Mean

                S.D.

                Median

                N*

                Mean

                S.D.

                Median

                Wilcoxon p-value

                Supp. Vitamin A (IU)

                1750

                2965.2

                2801.5

                3571.4

                5071

                2789.8

                2845.7

                3571.4

                0.006

                Supp. Vitamin A (mcg RAE)

                1750

                889.6

                840.4

                1071.4

                5071

                836.9

                853.7

                1071.4

                0.006

                Supp. Beta Carotene

                1750

                350.6

                329.0

                428.6

                5071

                325.1

                323.0

                428.6

                0.002

                Supp. Vitamin E

                1750

                52.6

                113.6

                20.1

                5071

                50.8

                108.8

                20.1

                0.046

                Supp. Vitamin C

                1750

                140.5

                273.5

                60.0

                5071

                134.4

                262.3

                60.0

                0.076

                Supp. Thiamin (mg)

                1750

                1.4

                2.0

                1.5

                5071

                1.3

                1.9

                1.1

                0.002

                Supp. Riboflavin (mg)

                1750

                1.3

                1.5

                1.7

                5071

                1.2

                1.5

                1.2

                0.002

                Supp. Niacin (mg)

                1750

                13.7

                13.4

                20.0

                5071

                12.7

                12.9

                14.3

                0.003

                Supp. Vitamin B6 (mg)

                1750

                4.4

                10.6

                2.0

                5071

                4.3

                10.8

                1.4

                0.014

                Supp. Folic Acid (mcg)

                1750

                230.2

                191.8

                285.7

                5071

                215.8

                194.8

                285.7

                0.004

                Supp. Vitamin B12 (mcg)

                1750

                3.3

                2.8

                4.3

                5071

                3.1

                2.8

                4.3

                0.002

                Supp. Vitamin D (mcg)

                1750

                286.6

                365.6

                16.6

                5071

                290.5

                371.6

                16.6

                0.866

                Supp. Calcium (mg)

                1750

                50.8

                47.3

                71.4

                5071

                47.1

                47.2

                28.6

                0.003

                Supp. Magnesium (mg)

                1750

                10.4

                10.3

                12.9

                5071

                9.9

                10.2

                12.9

                0.111

                Supp. Iron (mg)

                1750

                8.4

                8.2

                10.7

                5071

                7.9

                8.3

                4.3

                0.007

                Supp. Zinc (mg)

                1750

                1.0

                0.9

                1.4

                5071

                0.9

                0.9

                0.6

                0.003

                Supp. Copper (mg)

                1750

                221.4

                186.7

                285.7

                5071

                205.9

                188.0

                285.7

                0.002

                Supp. Selenium (mcg)

                1750

                0.6

                4.9

                0.0

                5071

                0.7

                5.4

                0.0

                0.375

                Supplement Users Only

                         

                Supp. Vitamin A (IU)

                1208

                4295.6

                2377.5

                5000.0

                3295

                4293.5

                2450.7

                5000.0

                0.931

                Supp. Vitamin A (mcg RAE)

                1208

                1288.7

                713.3

                1500.0

                3295

                1288.0

                735.2

                1500.0

                0.931

                Supp. Beta Carotene

                1201

                510.9

                275.4

                600.0

                3268

                504.4

                267.2

                600.0

                0.558

                Supp. Vitamin E

                1261

                73.1

                128.1

                20.1

                3465

                74.3

                124.8

                20.1

                0.468

                Supp. Vitamin C

                1314

                187.2

                301.5

                60.0

                3612

                188.6

                293.9

                60.0

                0.262

                Supp. Thiamin (mg)

                1228

                2.0

                2.1

                1.5

                3323

                1.9

                2.1

                1.5

                0.841

                Supp. Riboflavin (mg)

                1228

                1.9

                1.5

                1.7

                3323

                1.8

                1.4

                1.7

                0.841

                Supp. Niacin (mg)

                1231

                19.5

                11.8

                20.0

                3346

                19.2

                11.3

                20.0

                0.857

                Supp. Vitamin B6 (mg)

                1234

                6.2

                12.2

                2.0

                3366

                6.5

                12.7

                2.0

                0.634

                Supp. Vitamin B12 (mcg)

                1220

                330.2

                140.6

                400.0

                3310

                330.6

                142.0

                400.0

                0.954

                Supp. Folic Acid (mcg)

                1195

                4.9

                2.0

                6.0

                3238

                4.8

                2.0

                6.0

                0.697

                Supp. Vitamin D (mcg)

                941

                533.0

                342.5

                500.0

                2727

                540.2

                349.1

                500.0

                0.686

                Supp. Calcium (mg)

                1086

                81.9

                32.5

                100.0

                2936

                81.4

                32.5

                100.0

                0.681

                Supp. Magnesium (mg)

                1110

                16.4

                8.2

                18.0

                3059

                16.5

                8.0

                18.0

                0.290

                Supp. Iron (mg)

                1107

                13.2

                6.5

                15.0

                2998

                13.3

                6.6

                15.0

                0.908

                Supp. Zinc (mg)

                1086

                1.6

                0.6

                2.0

                2936

                1.6

                0.7

                2.0

                0.681

                Supp. Copper (mg)

                1195

                324.2

                133.1

                400.0

                3238

                322.5

                133.1

                400.0

                0.697

                Supp. Selenium (mcg)

                23

                42.9

                0.0

                42.9

                82

                42.9

                0.0

                42.9

                1.000

                *N refers to the number of participants

                Table 10

                Supplement intake by APOE4 genotype in males in the Personalized Medicine Research Project

                 

                With E4

                No E4

                 

                Nutrient

                N

                Mean

                S.D.

                Median

                N

                Mean

                S.D.

                Median

                Wilcoxon p-value

                Supp. Vitamin A (IU)

                1198

                2068.6

                2769.4

                0.0

                3146

                2234.1

                2781.4

                82.1

                0.047

                Supp. Vitamin A (mcg RAE)

                1198

                620.6

                830.8

                0.0

                3146

                670.2

                834.4

                24.6

                0.047

                Supp. Beta Carotene

                1198

                239.8

                301.6

                0.0

                3146

                262.4

                322.6

                9.9

                0.043

                Supp. Vitamin E

                1198

                34.0

                92.0

                0.3

                3146

                35.5

                94.2

                1.3

                0.118

                Supp. Vitamin C

                1198

                95.1

                220.8

                8.2

                3146

                105.0

                243.7

                17.1

                0.312

                Supp. Thiamin (mg)

                1198

                0.9

                1.5

                0.0

                3146

                0.9

                1.6

                0.0

                0.042

                Supp. Riboflavin (mg)

                1198

                0.8

                1.2

                0.0

                3146

                0.9

                1.3

                0.0

                0.042

                Supp. Niacin (mg)

                1198

                9.6

                13.0

                0.0

                3146

                10.5

                13.8

                0.3

                0.052

                Supp. Vitamin B6 (mg)

                1198

                2.3

                7.4

                0.0

                3146

                2.8

                8.4

                0.0

                0.029

                Supp. Folic Acid (mcg)

                1198

                156.8

                189.9

                0.0

                3146

                171.7

                194.1

                6.6

                0.020

                Supp. Vitamin B12 (mcg)

                1198

                2.3

                2.8

                0.0

                3146

                2.5

                2.8

                0.1

                0.020

                Supp. Vitamin D (mcg)

                1198

                66.8

                199.6

                0.0

                3146

                88.3

                228.9

                0.0

                0.010

                Supp. Calcium (mg)

                1198

                34.2

                45.6

                0.0

                3146

                37.4

                46.7

                0.0

                0.029

                Supp. Magnesium (mg)

                1198

                6.7

                9.0

                0.0

                3146

                7.4

                9.4

                0.0

                0.022

                Supp. Iron (mg)

                1198

                5.9

                8.1

                0.0

                3146

                6.5

                8.5

                0.0

                0.029

                Supp. Zinc (mg)

                1198

                0.7

                0.9

                0.0

                3146

                0.7

                0.9

                0.0

                0.029

                Supp. Copper (mg)

                1198

                151.4

                185.6

                0.0

                3146

                166.1

                189.4

                6.6

                0.020

                Supp. Selenium (mcg)

                1198

                1.1

                6.8

                0.0

                3146

                1.4

                7.6

                0.0

                0.242

                Supplement Users Only

                         

                Supp. Vitamin A (IU)

                568

                4362.9

                2482.6

                5000.0

                1589

                4423.2

                2373.4

                5000.0

                0.415

                Supp. Vitamin A (mcg RAE)

                568

                1308.9

                744.8

                1500.0

                1589

                1327.0

                712.0

                1500.0

                0.415

                Supp. Beta Carotene

                564

                509.4

                236.2

                600.0

                1587

                520.2

                268.8

                600.0

                0.653

                Supp. Vitamin E

                603

                67.5

                120.6

                20.1

                1665

                67.0

                121.0

                20.1

                0.690

                Supp. Vitamin C

                652

                174.8

                275.2

                60.0

                1768

                186.8

                300.7

                60.0

                0.890

                Supp. Thiamin (mg)

                573

                1.8

                1.8

                1.5

                1603

                1.8

                1.9

                1.5

                0.363

                Supp. Riboflavin (mg)

                573

                1.7

                1.3

                1.7

                1603

                1.8

                1.3

                1.7

                0.363

                Supp. Niacin (mg)

                583

                19.8

                12.2

                20.0

                1628

                20.3

                12.9

                20.0

                0.492

                Supp. Vitamin B6 (mg)

                579

                4.8

                10.1

                2.0

                1621

                5.4

                11.0

                2.0

                0.217

                Supp. Vitamin B12 (mcg)

                571

                329.0

                137.8

                400.0

                1610

                335.6

                136.4

                400.0

                0.244

                Supp. Folic Acid (mcg)

                558

                4.9

                2.0

                6.0

                1574

                5.0

                1.9

                6.0

                0.185

                Supp. Vitamin D (mcg)

                241

                331.9

                332.1

                250.0

                738

                376.4

                339.2

                285.7

                0.069

                Supp. Calcium (mg)

                489

                83.7

                30.8

                100.0

                1394

                84.4

                30.9

                100.0

                0.466

                Supp. Magnesium (mg)

                503

                15.8

                6.7

                18.0

                1431

                16.3

                7.1

                18.0

                0.260

                Supp. Iron (mg)

                505

                13.9

                6.6

                15.0

                1437

                14.1

                7.0

                15.0

                0.516

                Supp. Zinc (mg)

                489

                1.7

                0.6

                2.0

                1394

                1.7

                0.6

                2.0

                0.466

                Supp. Copper (mg)

                558

                325.0

                132.2

                400.0

                1574

                331.9

                129.1

                400.0

                0.185

                Supp. Selenium (mcg)

                31

                42.9

                0.0

                42.9

                103

                42.9

                0.0

                42.9

                1.000

                *N refers to the number of participants

                Discussion

                The dietary intake of participants in the Personalized Medicine Research Project (PMRP) is a useful resource to assist in studies regarding gene-diet interactions. Statistically significant findings were seen when analyzing the PMRP dietary data for differences associated with smoking, alcohol consumption, and the APOE genotype.

                The National Health and Nutrition Examination Survey (NHANES) is a survey that documents dietary intake on a yearly basis. Comparing the PMRP dietary intake of macronutrients with that of NHANES, the PMRP dietary intake is relatively similar. In ages eighteen and above, percent energy from protein, carbohydrates, total fat, and saturated fat are similar between the PMRP and NHANES. NHANES data revealed slightly higher food energy, cholesterol, natural folate, and sodium intake. PMRP intake was significantly higher for calcium [18]. This finding could be due to the higher consumption of dairy foods and vegetables associated the farming in Wisconsin.

                Differences have been seen in dietary intake between smokers and nonsmokers. Interactions between diet and smoking can lead to negative health outcomes. Findings of previous studies suggest that smokers consume less fiber, vegetables, whole grains, fruits but more bacon/luncheon meats, whole milk, and calories in general [3]. Smokers also are less likely than nonsmokers to consume vitamins, minerals and/or supplements [3]. Our results are generally consistent with previous findings. In PMRP, women who smoke have a lower intake of supplements and vitamins, and a higher intake in food energy, fat, cholesterol, and protein. Similarly, supplement intake was lower and alcohol consumption was higher in smoking males.

                Studies have shown the APOE gene to be associated with increased risk for coronary heart disease (CHD) and Alzheimer's Disease. Smoking increases the risk for CHD alone, but its interaction with the APOE4 genotype can cause an even higher risk [2]. This demonstrates a possible gene-environment interaction. Our findings suggest that females with the E4 allele have higher supplement intake and smokers with the E4 allele have slightly lower use. Males with the E4 allele have lower supplement intake, but higher use is seen in nonsmokers. These data suggest that people may have started supplement use to prevent diseases for which they have in increased risk (possibly due to family history) and these diseases are associated with APOE. Vitamin E supplementation has been shown to decrease the risk of some diseases and supplements are marketed directly to consumers for this purpose.

                One strength of the PMRP dietary intake data is the size of the cohort that the data includes. The relatively high response rate is another strength of the resource. However, there were some response limitations. For early participants, dietary data were collected several years after their initial enrollment. The initial 17,000 participants were enrolled within the first eighteen months after the project began in 2002. The first set of mailings was not sent until 2006. Approximately 4% of participants were deceased by the time the DHQs were mailed. 2.7% of participants were not able to be contacted. Males were less likely to respond to the questionnaire. Although this information should be considered, the percentages are quite low and do not present a strong impact on the collected data.

                Conclusions

                Detailed dietary history data are available for more than 11,000 adult participants in a biobank with DNA, plasma and serum samples linked to a comprehensive electronic health record. The cohort is representative of the population of central Wisconsin. The dietary intake data will be a valuable resource for studies of gene-environment interactions. The Diet History Questionnaire should be followed up with periodic updates to assess changes in intake over time. The PMRP welcomes collaboration to enhance and expand gene-environment research.

                Declarations

                Acknowledgements

                This research was funded in part by grant 1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources, National Institutes of Health. The authors acknowledge the contributions of Cathy Schneider and Carla Rottscheit to data collection and management.

                Authors’ Affiliations

                (1)
                Marshfield Clinic Research Foundation, Center for Human Genetics
                (2)
                Marshfield Clinic Research Foundation, Biomedical Informatics Research Center
                (3)
                Marshfield Clinic Research Foundation, Epidemiology Research Center

                References

                1. Tucker KL: Assessment of usual dietary intake in population studies of gene-diet interaction. Nutr Metab Cardiovasc Dis 2007, 17: 74–81.View Article
                2. Lussier-Cacan S, Bolduc A, Xhignesse M, Niyonsenga T, Sing CF: Impact of alcohol intake on measures of lipid metabolism depends on context defined by gender, body mass index, cigarette smoking, and Apolipoprotein E genotype. Arterioscler Thromb Vasc Biol 2002, 22: 824–831.View Article
                3. Subar AF, Harlan LC, Mattson ME: Food and nutrient intake differences between smokers and non-smokers in the US. Am J Publ Health 1990, 80: 1323–1329.View Article
                4. Talmund PJ, Humphries SE: Gene:Environment interactions and coronary heart disease risk. World Rev Nutr Diet 2004, 93: 29–40.View Article
                5. Talmud PJ: How to identify gene-environment interactions in a multifactorial disease: CHD as an example. Proc Nutr Soc 2004, 63 (1) : 5–10.View Article
                6. Eichner JE, Kuller LH, Ferrell RE, Meilahn EN, Kamboh MI: Phenotypic effects of apolipoprotein structural variation on lipid profiles. III. Contribution of apolipoprotein E phenotype to prediction of total cholesterol, apolipoprotein B, and low density lipoprotein cholesterol in the healthy women study. Arteriosclerosis 1990, 10: 379–385.View Article
                7. Boerwinkle E, Utermann G: Simultaneous effects of the apolipoprotein E polymorphism on apolipoprotein E, apolipoprotein B, and cholesterol metabolism. Am J Hum Genet 1988, 42: 104–112.
                8. McCarty CA, Wilke RA, Giampietro PF, Wesbrook SD, Caldwell MD: The Marshfield Clinic Personalized Medicine Research Project (PMRP): design, methods and recruitment for a large population-based biobank. Personalized Med 2005, 2: 49–79.View Article
                9. McCarty CA, Mukesh BN, Giampietro PF, Wilke RA: Healthy People 2010 prevalence in the Marshfield Clinic Personalized Medicine Research Project: opportunities for public health genomics research. Personalized Med 2007, 4: 183–190.View Article
                10. McCarty CA, Peissig P, Caldwell MD, Wilke RA: The Marshfield Clinic Personalized Medicine Research Project: 2008 scientific update and lessons learned in the first 6 years. Personalized Med 2008, 5: 529–541.View Article
                11. Cross DS, Ivacic LC, McCarty CA: Development of a fingerprinting panel using medically relevant polymorphisms. BMC Med Genom 2009, 2: 17.View Article
                12. Subar AF, Thompson FE, Kipnis V, Midthune D, Hurwitz P, McNutt S, McIntosh A, Rosenfeld S: Comparative validation of the Block, Willett, and National Cancer Institute food frequency questionnaires. The Eating at America's Table Study. Am J Epidemiol 2001, 154: 1089–1099.View Article
                13. Schatzkin A, Kipnis V, Carroll RJ, Midthune D, Subar AF, Bingham S, Schoeller DA, Troiano RP, Freedman LS: A comparison of a food frequency questionnaire with a 24-hour recall for use in an epidemiological cohort study: results from the biomarker-based Observing Protein and Energy Nutrition (OPEN) study. In J Epidemiol 2003, 32: 1054–1062.View Article
                14. Millen AE, Midthune D, Thompson FE, Kipnis V, Subar AF: The National Cancer Institute Diet History Questionnaire: validation of pyramid food servings. Am J Epidemiol 2005, 163: 279–288.View Article
                15. Dixon LB, Subar AF, Wideroff L, Thompson FE, Kahle LL, Potischman N: Carotenoid and tocopheral estimates from the NCI Dietary History Questionnaire are valid compared with multiple recalls and serum biomarkers. J Nutr 2006, 136: 3054–3061.
                16. Flood A, Subar AF, Hull SG, Zimmerman TP, Jenkins DJA, Schatzkin A: Methodology for adding glycemic load values to the National Cancer Institute Diet History Questionnaire database. J Am Diet Assoc 2006, 106: 393–402.View Article
                17. Thompson FE, Kipnis V, Midthune D, Freedman LS, Carroll RJ, Subar AF, Brown CC, Butcher MS, Mouw T, Leitzmann M, Schatzkin A: Performance of a food-frequency questionnaire in the US NIH-AARP (National Institutes of Health-American Association of Retired Persons) Diet and Health Study. Publ Health Nutr 2007, 11: 183–195.
                18. Wright JD, Wang CY, Kennedy-Stephenson J, Ervin RB: Dietary intake of ten key nutrients for public health, United States: 1999–2000. Adv Data 2003, 334: 1–4.

                Copyright

                © Strobush et al; licensee BioMed Central Ltd. 2011

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​2.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.