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 language | English |
|---|---|
| Pages (from-to) | 207-214 |
| Number of pages | 8 |
| Journal | Journal of Steroid Biochemistry and Molecular Biology |
| Volume | 144 |
| Issue number | PART A |
| DOIs | |
| State | Published - 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
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 journal › Review article
}
TY - JOUR
T1 - DNA methylation levels of CYP2R1 and CYP24A1 predict vitamin D response variation
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.
PY - 2014
Y1 - 2014
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'.
AB - 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'.
UR - http://www.scopus.com/inward/record.url?scp=84906789954&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906789954&partnerID=8YFLogxK
U2 - 10.1016/j.jsbmb.2013.10.004
DO - 10.1016/j.jsbmb.2013.10.004
M3 - Review article
VL - 144
SP - 207
EP - 214
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
SN - 0960-0760
IS - PART A
ER -