Common Genetic Variations in the Vitamin D Pathway in Relation to Blood Pressure

Vitamin D is involved in blood pressure (BP) regulation. Genetic variations may influence the effect of vitamin D on BP, but data from epidemiologic studies remain inconsistent. We conducted a comprehensive genetic association study 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 genome-wide meta-analysis results from 69,395 men and women of European ancestry. First, we found none of 5 selected vitamin D-related candidate single nucleotide polymorphisms (SNPs) was associated with systolic BP (SBP) or diastolic BP (DBP). Second, in 61 candidate SNPs involved in vitamin D metabolism and signaling, rs1507023 (in RBFOX1) and rs2296241 (in CYP24A1) showed significant associations with SBP, DBP, mean arterial pressure, or pulse pressure in the WGHS before, but not after, multiple testing corrections. Nominally significant associations in the ICBP were also not significant after corrections. Third, among 24 candidate genes across vitamin D pathway, associations with BP traits that meet gene-wide significance level were found for NCOA3 (rs2235734), RXRA (rs875444), DHCR7 (rs1790370), VDR (rs2544037), and NCOR2 (rs1243733, rs1147289) in the WGHS and NCOR1, TP53BP1, and TYRP1 in the ICBP. However, none of these associations reached significance threshold in both studies. Our study did not replicate previously observed associations of vitamin D-related SNPs with BP. There was suggestive evidence for associations in other vitamin D pathway genes; however, these associations either did not reach the significance threshold or were not replicated.