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

  • Lacie Strobush1,
  • Richard Berg2,
  • Deanna Cross1,
  • Wendy Foth1,
  • Terrie Kitchner1,
  • Laura Coleman3 and
  • Catherine A McCarty1Email author
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.
https://static-content.springer.com/image/art%3A10.1186%2F1475-2891-10-13/MediaObjects/12937_2010_Article_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)
Center for Human Genetics, Marshfield Clinic Research Foundation
(2)
Biomedical Informatics Research Center, Marshfield Clinic Research Foundation
(3)
Epidemiology Research Center, Marshfield Clinic Research Foundation

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© Strobush et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. 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.

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