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Genetic polymorphisms of the vitamin D binding protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women

¹ From the Département de Médecine Sociale et Préventive, Université Laval, Québec, Canada (MS, CD, and JB); the Unité de Recherche en Santé des Populations, Centre Hospitalier Affilié Universitaire de Québec, Québec, Canada (MS, CD, SB, and JB); the Centre des Maladies du sein Deschênes-Fabia, Centre Hospitalier Affilie Universitaire de Québec, Québec, Canada (CD, SB, and JB); and the Cancer Prevention Research Unit, Lady Davis Institute of the Jewish General Hospital and McGill University, Departments of Medicine and Oncology, Montréal, Canada (MP).

² Supported in part by grant 4811-82 from the Canadian Breast Cancer Research Alliance, a grant from the Translation Acceleration Grants Program for Breast Cancer Control of the Canadian Breast Cancer Research Alliance and the Canadian Institutes of Health Research. MS was supported by studentships from the Canadian Institutes of Health Research and National Cancer Institute of Canada. CD was supported by a postdoctoral fellowships from the Cancer Research Society Inc and the Canadian Institutes of Health Research.

³ Reprints not available. Address correspondence to C Diorio, Unité de Recherche en Santé des Populations, Hôpital du Saint-Sacrement du Centre Hospitalier Affilié Universitaire de Québec, 1050 Chemin Sainte-Foy, Québec, Canada G1S 4L8. E-mail: caroline.diorio{at}uresp.ulaval.ca.

Background: Vitamin D status, determined on the basis of 25-hydroxyvitamin D [25(OH)D] concentrations, is associated with the risk of several diseases. Vitamin D binding protein (DBP) is the major carrier of vitamin D and its metabolites, but the role of DBP single nucleotide polymorphisms (SNPs) on 25(OH)D concentrations is unclear.

Objective: The objective was to evaluate the association of 2 DBP gene SNPs with 25(OH)D concentrations and explore whether such association varies according to the amount of vitamin D that needs to be transported.

Design: This cross-sectional study included 741 premenopausal white women, mostly of French descent. Plasma 25(OH)D concentrations were measured by radioimmunoassay. DBP-1 (rs7041) and DBP-2 (rs4588) were genotyped with a Sequenom MassArray platform. Associations and interactions were modeled by using multivariate linear regression.

Results: DBP-1 and DBP-2 SNPs were in strong linkage disequilibrium and were both associated with 25(OH)D concentrations. An additional copy of the rare allele of DBP-1 or DBP-2 was associated with lower 25(OH)D concentrations (β = –3.29, P for trend = 0.0003; β = –4.22, P for trend < 0.0001, respectively). These DBP polymorphisms explained as much of the variation in circulating 25(OH)D as did total vitamin D intake (r² = 1.3% for DBP-1, r² = 2.0% for DBP-2, and r² 1.2% for vitamin D intake).

Conclusion: Circulating 25(OH)D concentrations in premenopausal women are strongly related to DBP polymorphisms. Whether DBP rare allele carriers have a different risk of vitamin D–related diseases and whether such carriers can benefit more or less from dietary interventions, vitamin D supplementation, or sun exposure need to be clarified.

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