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

Yu Zhou, Lan Juan Zhao, Xiaojing Xu, An Ye, Dianne Travers-Gustafson, Boting Zhou, Hong Wei Wang, Weidong Zhang, L. Lee Hamm, Hong Wen Deng, Robert R. Recker, Joan M. Lappe

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Abstract

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 (1100 IU/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 <0.05). For CYP24A1, baseline DNA methylation levels at two CpG sites were also negatively associated with vitamin D response variation (r = -0.151, P = 0.011; r = -0.131, P = 0.025). These negative associations were consistent with the first study's results. Our findings indicate that baseline DNA methylation levels of CYP2R1 and CYP24A1 may predict vitamin D response variation. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.

Original languageEnglish
Pages (from-to)207-214
Number of pages8
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume144
Issue numberPART A
DOIs
StatePublished - 2014

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Cell Biology
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Molecular Medicine

Cite this

Zhou, Y., Zhao, L. J., Xu, X., Ye, A., Travers-Gustafson, D., Zhou, B., Wang, H. W., Zhang, W., Lee Hamm, L., Deng, H. W., Recker, R. R., & Lappe, J. M. (2014). DNA methylation levels of CYP2R1 and CYP24A1 predict vitamin D response variation. Journal of Steroid Biochemistry and Molecular Biology, 144(PART A), 207-214. https://doi.org/10.1016/j.jsbmb.2013.10.004