A prospective study of plasma vitamin D metabolites, vitamin D receptor gene polymorphisms, and risk of hypertension in men.

PURPOSE: Laboratory studies have suggested that vitamin D inadequacy may be implicated in development of hypertension. Evidence from epidemiologic studies remains limited. We aim to examine the prospective associations of circulating vitamin D metabolites, vitamin D receptor (VDR) gene polymorphisms, and their interaction with risk of hypertension.

METHODS: We conducted prospective analyses among 1,211 US men that were free of baseline hypertension and had baseline plasma 25hydroxy-vitamin D (25(OH)D) or 1,25dihydroxy-vitamin D (1,25(OH)2D) measured and VDR BsmI or FokI polymorphisms genotyped.

RESULTS: During 15.3-year follow-up, 695 men developed incident hypertension. After multivariable adjustment, the hazard ratios (HRs) and 95 % CIs for hypertension across increasing quartiles of plasma vitamin D metabolites were 1.00 (ref), 0.94 (0.69-1.27), 0.69 (0.50-0.96), and 0.82 (0.60-1.13) for 25(OH)D (p, trend: 0.43), and 1.00, 0.92 (0.66-1.27), 1.12 (0.82-1.54), and 1.19 (0.86-1.63) for 1,25(OH)2D (p, trend: 0.16). Compared with carriers of VDR BsmI bb, carriers of bB or BB had a HR of 1.25 (1.04-1.51) for hypertension. For VDR FokI polymorphism, compared with carriers of FF and Ff combined, carriers of ff had a HR of 1.32 (1.03-1.70). The relation between plasma 25(OH)D and risk of hypertension did not differ by VDR BsmI and FokI polymorphisms.

CONCLUSIONS: In a prospective cohort of men, we found suggestive evidence for an inverse association between plasma 25(OH)D and risk of hypertension. We also found associations between VDR BsmI and FokI polymorphisms with hypertension risk. More research is needed to further determine the role of vitamin D in hypertension prevention.