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Race/Ethnicity-Specific Association of Vitamin D and Global DNA Methylation: Cross-Sectional and Interventional Findings

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) vita...

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Autores principales: Zhu, Haidong, Bhagatwala, Jigar, Huang, Ying, Pollock, Norman K., Parikh, Samip, Raed, Anas, Gutin, Bernard, Harshfield, Gregory A., Dong, Yanbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822838/
https://www.ncbi.nlm.nih.gov/pubmed/27049643
http://dx.doi.org/10.1371/journal.pone.0152849
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author Zhu, Haidong
Bhagatwala, Jigar
Huang, Ying
Pollock, Norman K.
Parikh, Samip
Raed, Anas
Gutin, Bernard
Harshfield, Gregory A.
Dong, Yanbin
author_facet Zhu, Haidong
Bhagatwala, Jigar
Huang, Ying
Pollock, Norman K.
Parikh, Samip
Raed, Anas
Gutin, Bernard
Harshfield, Gregory A.
Dong, Yanbin
author_sort Zhu, Haidong
collection PubMed
description 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, 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 MethylFlash(TM) 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 D(3) 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.
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spelling pubmed-48228382016-04-22 Race/Ethnicity-Specific Association of Vitamin D and Global DNA Methylation: Cross-Sectional and Interventional Findings Zhu, Haidong Bhagatwala, Jigar Huang, Ying Pollock, Norman K. Parikh, Samip Raed, Anas Gutin, Bernard Harshfield, Gregory A. Dong, Yanbin PLoS One Research Article 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, 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 MethylFlash(TM) 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 D(3) 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. Public Library of Science 2016-04-06 /pmc/articles/PMC4822838/ /pubmed/27049643 http://dx.doi.org/10.1371/journal.pone.0152849 Text en © 2016 Zhu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhu, Haidong
Bhagatwala, Jigar
Huang, Ying
Pollock, Norman K.
Parikh, Samip
Raed, Anas
Gutin, Bernard
Harshfield, Gregory A.
Dong, Yanbin
Race/Ethnicity-Specific Association of Vitamin D and Global DNA Methylation: Cross-Sectional and Interventional Findings
title Race/Ethnicity-Specific Association of Vitamin D and Global DNA Methylation: Cross-Sectional and Interventional Findings
title_full Race/Ethnicity-Specific Association of Vitamin D and Global DNA Methylation: Cross-Sectional and Interventional Findings
title_fullStr Race/Ethnicity-Specific Association of Vitamin D and Global DNA Methylation: Cross-Sectional and Interventional Findings
title_full_unstemmed Race/Ethnicity-Specific Association of Vitamin D and Global DNA Methylation: Cross-Sectional and Interventional Findings
title_short Race/Ethnicity-Specific Association of Vitamin D and Global DNA Methylation: Cross-Sectional and Interventional Findings
title_sort race/ethnicity-specific association of vitamin d and global dna methylation: cross-sectional and interventional findings
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822838/
https://www.ncbi.nlm.nih.gov/pubmed/27049643
http://dx.doi.org/10.1371/journal.pone.0152849
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