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

Journal: The Journal of steroid biochemistry and molecular biology 2014;144 Pt A():207-14

PMID: 24128439

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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 (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<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'.

Address: Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, Tulane University, New Orleans, LA 70112, USA; Cell and Molecular Biology Department, Tulane University, New Orleans, LA 70118, USA.; Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, Tulane University, New Orleans, LA 70112, USA; Osteoporosis Research Center, Creighton University, Omaha, NE 68131, USA. Electronic address: [email protected].; Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, Tulane University, New Orleans, LA 70112, USA; Osteoporosis Research Center, Creighton University, Omaha, NE 68131, USA.; Osteoporosis Research Center, Creighton University, Omaha, NE 68131, USA.; Department of Pharmacy, Xiang-Ya Hospital of Central South University, Changsha, Hunan, China.; Department of Medicine, University of Chicago, Chicago, IL 60637, USA.; Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, Tulane University, New Orleans, LA 70112, USA.; School of Medicine, Tulane University, New Orleans, LA, 70112, USA.

DOI: 10.1016/j.jsbmb.2013.10.004

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MeSH Terms: Cholestanetriol 26-Monooxygenase, Cytochrome P450 Family 2, DNA Methylation, Female, Genetic Variation, Humans, Randomized Controlled Trials as Topic, Steroid Hydroxylases, Vitamin D, Vitamin D3 24-Hydroxylase, Vitamins