title: Race/Ethnicity-Specific Association of Vitamin D and Global DNA Methylation: Cross-Sectional and Interventional Findings.
abstract: OBJECTIVE
  Understanding of the influence of vitamin D deficiency on epigenome will provide novel insights into the chronic disease risk. We tested our hypotheses that 1) vitamin D deficiency is associated with global hypomethylation and this association may be race/ethnicity dependent; and 2) vitamin D supplementation will increase global DNA methylation level.
  
  
  METHODS
  A two-stage design, cross-sectional observation followed by a 16 week randomized, double- blinded, placebo-controlled trial (RCT) of vitamin D3 supplementation, was undertaken. Global DNA methylation level (percentage of 5-methylcytosine, %5-mC) was quantified using leukocyte DNA with the MethylFlashTM Methylated DNA Quantification kit (Epigentek). Global methylation data was obtained from 454 Caucasians and African Americans (42%) in the observation cohort and 58 African Americans with vitamin D deficiency in the dose responsive RCT.
  
  
  RESULTS
  In the cross-sectional study, African Americans had lower %5-mC than Caucasians (P = 0.04). A significant interaction was detected between plasma 25(OH)D and race on %5-mC (P = 0.05), as a positive association was observed between plasma 25(OH)D and %5-mC in African Americans (β = 0.20, p<0.01), but not in Caucasians (β = 0.03, p = 0.62). In the 16-week RCT, a dose-response benefit of vitamin D3 supplementation was observed for %5-mC, as indicated by a significant linear upward trend (-0.01 ± 0.01%, placebo; 0.11 ± 0.01%, ~600 IU/day; 0.30 ± 0.01%, ~2,000 IU/day; and 0.65 ± 0.01%, ~4,000 IU/day group; P-trend = 0.04).
  
  
  CONCLUSIONS
  Vitamin D deficiency is associated with global hypomethylation in African Americans. Vitamin D3 supplementation increases global DNA methylation in a dose-response manner in African Americans with vitamin D deficiency.
authors.affiliation: Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Haidong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.|Internal Medicine, Department of Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Jigar
authors.initials: J
authors.lastname: Bhagatwala
authors.affiliation: Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Norman K
authors.initials: NK
authors.lastname: Pollock
authors.affiliation: Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.|Internal Medicine, Department of Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Samip
authors.initials: S
authors.lastname: Parikh
authors.affiliation: Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.|Internal Medicine, Department of Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Anas
authors.initials: A
authors.lastname: Raed
authors.affiliation: Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Bernard
authors.initials: B
authors.lastname: Gutin
authors.affiliation: Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Harshfield
authors.affiliation: Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D004311:Double-Blind Method; D005006:Ethnicity; D005260:Female; D006801:Humans; D008297:Male; D010919:Placebos; D044469:Racial Groups; D014807:Vitamin D / Q000378:metabolism*
chemical_list: D010919:Placebos; D014807:Vitamin D