DNA methylation levels of CYP2R1 and CYP24A1 predict vitamin D response variation

• Published in: The Journal of steroid biochemistry and molecular biology 2014-10, Vol.144, p.207-214
• Main Authors: Zhou, Yu, Zhao, Lan-Juan, Xu, Xiaojing, Ye, An, Travers-Gustafson, Dianne, Zhou, Boting, Wang, Hong-Wei, Zhang, Weidong, Lee Hamm, L., Deng, Hong-Wen, Recker, Robert R., Lappe, Joan M.
• Format: Article
• Language: English
• Subjects: Cholestanetriol 26-Monooxygenase - genetics; CYP24A1; CYP2R1; Cytochrome P450 Family 2; DNA Methylation; Female; Genetic Variation; Humans; Methylation; Randomized Controlled Trials as Topic; Steroid Hydroxylases - genetics; Vitamin D - administration & dosage; Vitamin D - analogs & derivatives; Vitamin D - blood; Vitamin D response variation; Vitamin D3 24-Hydroxylase; Vitamins - administration & dosage; Vitamins - blood
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2013.10.004

•We examined the methylation levels of CYPs family in patients who had vitamin D supplementation.•Baseline methylation level of CYP2R1 is negatively associated with vitamin D response variation.•Baseline methylation level of CYP24A1 is negatively associated with vitamin D response variation.•Baseline DNA methylation levels of CYP2R1 and CYP24A1 may predict vitamin D response variation. Factors contributing to the variability of serum 25-hydroxyvitamin D [25(OH)D] in response to a given dose of vitamin D supplementation are largely unknown. We examined whether DNA methylation levels of Cytochrome P450 (CYP) enzymes (CYP2R1, CYP24A1, CYP27A1, and CYP27B1) are potential biomarkers predicting vitamin D response variation. We randomized 446 white postmenopausal women to a calcium and vitamin D (1100IU/day) intervention for at least 12 months. From these subjects, 18 with the highest 12-month increase in serum 25(OH)D were selected as “responders.” Another 18 with the lowest 12-month increase in serum 25(OH)D were selected as “non-responders.” DNA methylation levels between the groups were compared. To validate findings in the first study, association between DNA methylation levels and vitamin D response variation was studied in another 145 extended independent white postmenopausal women. In the first study, compared to non-responders, responders had significantly lower baseline DNA methylation levels in the promoter region of CYP2R1 (8% in the responders vs. 30% in the non-responders, P=0.004), and CYP24A1 (13% in the responders vs. 32% in the non-responders, P=0.001). In the validation study, for CYP2R1, baseline DNA methylation levels at eight CpG sites were negatively associated with 12-month increases in serum 25(OH)D (P