Race/ethnicity-specific association of Vitamin D and global DNA methylation: Cross-sectional and interventional findings

Haidong Zhu, Jigar Bhagatwala, Ying Huang, Norman K. Pollock, Samip Parikh, Anas Raed, Bernard Gutin, Gregory A Harshfield, Yanbin Dong

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere0152849
JournalPloS one
Volume11
Issue number4
DOIs
StatePublished - Apr 1 2016

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vitamin D deficiency
DNA methylation
DNA Methylation
African Americans
nationalities and ethnic groups
vitamin D
Vitamin D Deficiency
Vitamin D
Association reactions
Cholecalciferol
cholecalciferol
placebos
dose response
5-Methylcytosine
Ergocalciferols
Plasmas
Placebos
Observation
Methylation
ergocalciferol

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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.

In: PloS one, Vol. 11, No. 4, e0152849, 01.04.2016.

Research output: Contribution to journalArticle

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abstract = "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.",
author = "Haidong Zhu and Jigar Bhagatwala and Ying Huang and Pollock, {Norman K.} and Samip Parikh and Anas Raed and Bernard Gutin and Harshfield, {Gregory A} and Yanbin Dong",
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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

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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.

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