Epigenetics Predicts Serum 25-Hydroxyvitamin D Response to Vitamin D₃ Supplementation in African Americans

Scope: The effects of vitamin D₃ supplementations on circulating 25-hydroxyvitamin D [25(OH)D] are varied. The hypothesis that the baseline DNA methylation plays a role in the serum 25(OH)D response to vitamin D₃ supplementation is tested. Methods and results: A randomized clinical trial is first conducted among 64 African Americans, who are randomly assigned to a placebo or a 16-week treatment of 600, 2000, and 4000 IU d^–1 of vitamin D₃ supplements. Expected serum 25(OH)D concentrations at posttest are estimated by intervention, age, gender, body mass index, baseline 25(OH)D concentrations, and seasonal variations. The 25(OH)D response is categorized into a high-response group when the actual 25(OH)D concentrations at posttest are higher than expected, and a low-response group otherwise. The 25(OH)D response is associated with baseline methylation levels of CYP family and VDR genes (raw p < 0.05). At a genome-wide level, the baseline methylation level of cg07873128 (OSBPL5) that regulates cholesterol balance and calcium homeostasis is higher in the low-response group (false discovery rate = 0.028). Conclusions: The baseline methylation levels of CYP family and VDR modulate 25(OH)D response. In addition, the hypermethylation of cg07873128 at the baseline, which is located in the imprinted gene OSBPL5, may reduce the serum 25(OH)D response to vitamin D₃ supplementation.