Vitamin D Metabolism-Related Gene Haplotypes and Their Association with Metabolic Disturbances Among African-American Urban Adults

Abstract

Epidemiological studies have confirmed associations of the vitamin D receptor (VDR) and vitamin D-related gene polymorphisms with adiposity and other metabolic disturbances. Those associations may be sex-specific. We evaluated the cross-sectional and longitudinal relationships between metabolic disturbances and haplotypes constructed from single nucleotide polymorphisms of VDR (BsmI:G/A: rs1544410; ApaI:A/C: rs7975232; and TaqI:G/A: rs731236) and MEGALIN (rs3755166:G/A; rs2075252:C/T and rs2228171:C/T) genes, in a sample of African-American adults. From 1,024 African Americans participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS, 2004–2013, Baltimore, MD), our analyses included 539 participants with complete genetic, baseline covariate and metabolic outcome data (at baseline and follow-up). Mean ± SD period of follow-up was 4.64 ± 0.93 y. Multivariable-adjusted Cox proportional hazards and logistic regression models were conducted. Among key findings, in men, incident hypertension was inversely related to MEGALIN₁ (GCC), [HR = 0.45, 95% CI: 0.23–0.90, p = 0.024]. Overall, there was a direct, linear dose-response association between VDR₂ (AAG: BAt) and MetS at baseline [OR = 1.60, 95% CI: 1.11–2.31, p = 0.012], while among men, VDR₃ (GAA: bAT) was inversely related to baseline MetS [OR = 0.40, 95% CI: 0.19–0.81, p = 0.011]. In conclusion, VDR and MEGALIN gene variations can affect prevalent MetS and the incidence rate of hypertension, respectively, among African-American urban adults.