Vitamin D receptor gene polymorphisms are associated with adiposity phenotypes123

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Background: Emerging data suggest a role for the vitamin D receptor (VDR) in lipogenesis and adipocyte differentiation.

Objective: Our objective was to evaluate the association of VDR gene variants and adiposity phenotypes in an epidemiologic study.

Design: In a sample of 1773 healthy female adults recruited from western New York, we tested for the association of 14 VDR single nucleotide polymorphisms (SNPs) with the following 3 adiposity phenotypes: body mass index (in kg/m2), waist circumference (in cm), and abdominal height (in cm). We examined age, education, total energy intake, smoking status, alcohol intake, and menopausal status as potential covariates.

Results: One SNP, rs3782905, remained associated with all 3 adiposity phenotypes after multiple-testing correction (Bonferroni-adjusted P = 0.004). The mean waist circumference for women with the rs3782905 homozygous rare genotype was 4.4 cm larger than for women with the common homozygous genotype. Two other VDR SNPs were associated with waist circumference and abdominal height, but the associations did not survive multiple-testing correction. Adjustment for covariates did not influence the results.

Conclusion: The study results and the biological activity of VDR in adipocyte differentiation suggest that 3′ VDR variants may play a role in adiposity phenotypes.

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1

From the Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY (HMO-B, RC, AEM, MT, and JLF), and the Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC (PGS and CM).

2

Supported by funds from the New York State Department of Health, New York State Breast Cancer Research and Education Fund (contract C020920 to AM), the Department of Social and Preventive Medicine and the Center of Excellence in Bioinformatics and Life Sciences at the University at Buffalo (to HMO-B), the Department of Defense (grants DAMD 170310446 and 170010417), and the National Institutes of Health (grants K07CA136969, R01CA092040, and P50AA09802).

3

Address correspondence to HM Ochs-Balcom, Department of Social and Preventive Medicine, 270 Farber Hall, University at Buffalo, Buffalo, NY 14214-8001. E-mail: [email protected].