Abstract P257: Common Genetic Variations in the Vitamin D Pathway in Relation to Blood Pressure
Background: Vitamin D is involved in the regulation of blood pressure (BP) through multiple mechanisms. Genetic variation may influence the effect of vitamin D on BP, but data from epidemiologic studies remain limited.
Methods: We conducted a comprehensive genetic association study to investigate the variants in an expanded vitamin D metabolism and signaling pathway in relation to BP. Analyses were conducted in the Women’s Genome Health Study (WGHS) with genome-wide genotype data among 23,294 women of European ancestry and in the International Consortium of Blood Pressure (ICBP) with published genome-wide meta-analysis results from 69,395 men and women of European ancestry.
Results: Analyses were conducted in three stages. First, among 5 candidate single-nucleotide polymorphisms (SNPs) in the vitamin D related genes that were previously found associated with BP, none was associated with systolic (SBP) or diastolic BP (DBP) in the WGHS or ICBP. Second, in an expanded set of 61 SNPs involved in vitamin D metabolism and signaling pathway, rs1507023 (in RBFOX1) and rs2296241 (in CYP24A1) showed nominally significant associations with SBP, DBP, mean arterial pressure (MAP), or pulse pressure (PP) in the WGHS, but the associations were no longer significant after correction for multiple hypothesis testing. Similarly, nominally significant associations found in the ICBP were also not significant after multiple testing corrections. Third, among 24 candidate genes across the vitamin D pathway, associations with BP traits that meet gene-wide significance level (gene-based empirical p<0.05) were found in the WGHS for NCOA3 (rs2235734), RXRA (rs875444), DHCR7 (rs1790370), VDR (rs2544037), and NCOR2 (rs1243733 and rs1147289). Similar gene-wide significant associations (gene-based p<0.05) with SBP or DBP were found in the ICBP for NCOR1, TP53BP1 and TYRP1. After further correction for number of genes in the pathway, however, only the association of TYRP1 with SBP in the ICBP reached significance threshold. Further, the WGHS observed associations were not replicated in the ICBP, and vice versa.
Conclusions: Our study in large samples of Caucasian population did not replicate several previously observed associations of candidate SNPs in the vitamin D pathway with BP. However, we found suggestive evidence for associations of other vitamin D pathway gene variants with BP traits. Future studies are needed to replicate our findings.
Author Disclosures: L. Wang: None. A. Chu: None. J.E. Buring: None. P.M. Ridker: None. D.I. Chasman: None. H.D. Sesso: None.
- © 2014 by American Heart Association, Inc.