TY - JOUR
T1 - Race/ethnicity-specific association of Vitamin D and global DNA methylation
T2 - Cross-sectional and interventional findings
AU - Zhu, Haidong
AU - Bhagatwala, Jigar
AU - Huang, Ying
AU - Pollock, Norman K.
AU - Parikh, Samip
AU - Raed, Anas
AU - Gutin, Bernard
AU - Harshfield, Gregory A
AU - Dong, Yanbin
N1 - Publisher Copyright:
© 2016 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/4
Y1 - 2016/4
N2 - Objectives: 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, doubleblinded, 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 MethylFlash™ 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.
AB - Objectives: 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, doubleblinded, 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 MethylFlash™ 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.
UR - http://www.scopus.com/inward/record.url?scp=84962787233&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962787233&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0152849
DO - 10.1371/journal.pone.0152849
M3 - Article
C2 - 27049643
AN - SCOPUS:84962787233
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 4
M1 - e0152849
ER -