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Title: Genome-wide association study of circulating vitamin D-binding protein.
Authors: Moy KA,  Mondul AM,  Zhang H,  Weinstein SJ,  Wheeler W,  Chung CC,  Männistö S,  Yu K,  Chanock SJ,  Albanes D
Journal: Am J Clin Nutr
Date: 2014 Apr 16
Branches: BB, CGR, LTG, NEB, OD
PubMed ID: 24740207
PMC ID: PMC4021784
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.