Genome-wide association study of circulating vitamin D-binding protein

Kristin A. Moy, Alison M. Mondul, Han Zhang, Stephanie J. Weinstein, William Wheeler, Charles C. Chung, Satu Männistö, Kai Yu, Stephen J. Chanock, Demetrius Albanes

Research output: Contribution to journalArticle

Abstract

Background: Vitamin D status may influence a spectrum of health outcomes, including osteoporosis, arthritis, cardiovascular disease, and cancer. Vitamin D-binding protein (DBP) is the primary carrier of vitamin D in the circulation and regulates the bioavailability of 25-hydroxyvitamin D. Epidemiologic studies have shown direct DBP-risk relations and modification by DBP of vitamin D-disease associations. Objective: We aimed to characterize common genetic variants that influence the DBP biochemical phenotype. Design: We conducted a genome-wide association study (GWAS) of 1380 men through linear regression of single-nucleotide polymorphisms (SNPs) in the Illumina HumanHap500/550/610 array on fasting serum DBP, assuming an additive genetic model, with adjustment for age at blood collection. Results: We identified 2 independent SNPs located in the gene encoding DBP, GC, that were highly associated with serum DBP: rs7041 (P = 1.42 × 10-246) and rs705117 (P = 4.7 × 10 -91). For both SNPs, mean serum DBP decreased with increasing copies of the minor allele: mean DBP concentrations (nmol/L) were 7335, 5149, and 3152 for 0, 1, and 2 copies of rs7041 (T), respectively, and 6339, 4280, and 2341, respectively, for rs705117 (G). DBP was also associated with rs12144344 (P = 5.9 × 10-7) in ST6GALNAC3. Conclusions: In this GWAS analysis, to our knowledge the first to examine this biochemical phenotype, 2 variants in GC-one exonic and one intronic-were associated with serum DBP concentrations at the genome-wide level of significance. Understanding the genetic contributions to circulating DBP may provide greater insights into the vitamin D binding, transport, and other functions of DBP and the effect of vitamin D status on health outcomes. The Alpha- Tocopherol, Beta-Carotene Cancer Prevention clinical trial was registered at clinicaltrials.gov as NCT00342992.

Original languageEnglish (US)
Pages (from-to)1424-1431
Number of pages8
JournalAmerican Journal of Clinical Nutrition
Volume99
Issue number6
DOIs
StatePublished - Jun 1 2014

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ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Moy, K. A., Mondul, A. M., Zhang, H., Weinstein, S. J., Wheeler, W., Chung, C. C., Männistö, S., Yu, K., Chanock, S. J., & Albanes, D. (2014). Genome-wide association study of circulating vitamin D-binding protein. American Journal of Clinical Nutrition, 99(6), 1424-1431. https://doi.org/10.3945/ajcn.113.080309