title: DNA methylation levels of CYP2R1 and CYP24A1 predict vitamin D response variation.
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'.
authors.affiliation: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: 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: lzhao2@tulane.edu.
authors.forename: Lan-Juan
authors.initials: LJ
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: An
authors.initials: A
authors.lastname: Ye
authors.affiliation: Osteoporosis Research Center, Creighton University, Omaha, NE 68131, USA.
authors.forename: Dianne
authors.initials: D
authors.lastname: Travers-Gustafson
authors.affiliation: Department of Pharmacy, Xiang-Ya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Boting
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wang
authors.affiliation: Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, Tulane University, New Orleans, LA 70112, USA.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Medicine, Tulane University, New Orleans, LA, 70112, USA.
authors.forename: L
authors.initials: L
authors.lastname: Lee Hamm
authors.affiliation: Center for Bioinformatics and Genomics, Department of Biostatistics and Bioinformatics, Tulane University, New Orleans, LA 70112, USA.
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
authors.affiliation: Osteoporosis Research Center, Creighton University, Omaha, NE 68131, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
authors.affiliation: Osteoporosis Research Center, Creighton University, Omaha, NE 68131, USA.
authors.forename: Joan M
authors.initials: JM
authors.lastname: Lappe
mesh_terms: D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics*; D000072467:Cytochrome P450 Family 2; D019175:DNA Methylation; D005260:Female; D014644:Genetic Variation; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D013250:Steroid Hydroxylases / Q000235:genetics*; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D065668:Vitamin D3 24-Hydroxylase; D014815:Vitamins / Q000008:administration & dosage / Q000097:blood*
chemical_list: D014815:Vitamins; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D013250:Steroid Hydroxylases; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase
keywords: CYP24A1; CYP2R1; Methylation; Vitamin D response variation