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

Research output: Contribution to journalReview article

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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

Fingerprint

DNA Methylation
Vitamin D
Serum
Cytochrome P-450 Enzyme System
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Validation Studies
Biomarkers
Vitamin D3 24-Hydroxylase
Genetic Promoter Regions
Association reactions
Calcium
Education

All Science Journal Classification (ASJC) codes

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

Cite this

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

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 144, No. PART A, 2014, p. 207-214.

Research output: Contribution to journalReview article

Zhou, Y, Zhao, LJ, Xu, X, Ye, A, Travers-Gustafson, D, Zhou, B, Wang, HW, Zhang, W, Lee Hamm, L, Deng, HW, Recker, RR & Lappe, JM 2014, 'DNA methylation levels of CYP2R1 and CYP24A1 predict vitamin D response variation', Journal of Steroid Biochemistry and Molecular Biology, vol. 144, no. PART A, pp. 207-214. https://doi.org/10.1016/j.jsbmb.2013.10.004
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. / DNA methylation levels of CYP2R1 and CYP24A1 predict vitamin D response variation. In: Journal of Steroid Biochemistry and Molecular Biology. 2014 ; Vol. 144, No. PART A. pp. 207-214.
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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'.",
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AU - Zhou, Yu

AU - Zhao, Lan Juan

AU - Xu, Xiaojing

AU - Ye, An

AU - Travers-Gustafson, Dianne

AU - Zhou, Boting

AU - Wang, Hong Wei

AU - Zhang, Weidong

AU - Lee Hamm, L.

AU - Deng, Hong Wen

AU - Recker, Robert R.

AU - Lappe, Joan M.

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N2 - 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'.

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