Unknown

Dataset Information

0

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


ABSTRACT: 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.We aimed to characterize common genetic variants that influence the DBP biochemical phenotype.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.We identified 2 independent SNPs located in the gene encoding DBP, GC, that were highly associated with serum DBP: rs7041 (P = 1.42 × 10?²??) and rs705117 (P = 4.7 × 10??¹). 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??) in ST6GALNAC3.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.

SUBMITTER: Moy KA 

PROVIDER: S-EPMC4021784 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Moy Kristin A KA   Mondul Alison M AM   Zhang Han H   Weinstein Stephanie J SJ   Wheeler William W   Chung Charles C CC   Männistö Satu S   Yu Kai K   Chanock Stephen J SJ   Albanes Demetrius D  

The American journal of clinical nutrition 20140416 6


<h4>Background</h4>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.<h4>Objective</h4>We aimed to characterize common genetic variants that influence the  ...[more]

Similar Datasets

| S-EPMC2883344 | biostudies-literature
| S-EPMC3168288 | biostudies-literature
| S-EPMC4839207 | biostudies-literature
| S-EPMC3209826 | biostudies-literature
| S-EPMC3648789 | biostudies-literature
| S-EPMC3467202 | biostudies-literature
| S-EPMC3366971 | biostudies-literature
| S-EPMC7050153 | biostudies-literature
| S-EPMC6829035 | biostudies-literature
| S-EPMC2667971 | biostudies-literature