Epigenetics Predicts Serum 25‐Hydroxyvitamin D Response to Vitamin D 3 Supplementation in African Americans

Scope The effects of vitamin D 3 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 D 3 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 D 3 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 D 3 supplementation.