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

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 MEGALIN(1) (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.