Homocysteine levels associate with subtle changes in leukocyte DNA methylation: an epigenome-wide analysis

被引：7

作者：

Mandaviya, Pooja R. ^{[1
,2
]}

Aissi, Dylan ^{[3
,4
]}

Dekkers, Koen F. ^{[5
]}

Joehanes, Roby ^{[6
]}

Kasela, Silva ^{[7
,8
]}

Vinh Truong ^{[9
]}

Stolk, Lisette ^{[2
]}

van Heemst, Diana ^{[10
,11
]}

Ikram, M. Arfan ^{[12
]}

Lindemans, Jan ^{[1
]}

Slagboom, P. Eline ^{[5
]}

Tregouet, David-Alexandre ^{[3
,4
]}

Uitterlinden, Andre G. ^{[2
]}

Wei, Chen ^{[13
]}

Wells, Phil ^{[14
]}

Gagnon, France ^{[9
]}

van Greevenbroek, Marleen M. J. ^{[15
,16
]}

Heijmans, Bastiaan T. ^{[5
]}

Milani, Lili ^{[7
]}

Morange, Pierre-Emmanuel ^{[17
,18
]}

van Meurs, Joyce B. J. ^{[2
]}

Heil, Sandra G. ^{[1
]}

机构：

[1] Erasmus Univ, Med Ctr, Dept Clin Chem, Rotterdam, Netherlands

[2] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands

[3] UPMC Univ Paris 06, Sorbonne Univ, INSERM, UMR S 1166,Team Genom & Pathophysiol Cardiovasc D, Paris, France

[4] ICAN Inst Cardiometab & Nutr, Paris, France

[5] Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, Mol Epidemiol Sect, Leiden, Netherlands

[6] Harvard Med Sch, Hebrew SeniorLife, Inst Aging Res, Boston, MA USA

[7] Univ Tartu, Estonian Genome Ctr, Tartu, Estonia

[8] Univ Tartu, Inst Mol & Cell Biol, Tartu, Estonia

[9] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada

[10] Leiden Univ, Med Ctr, Dept Gerontol, Leiden, Netherlands

[11] Leiden Univ, Med Ctr, Geriatr Sect, Leiden, Netherlands

[12] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands

[13] Tulane Univ, Dept Epidemiol, New Orleans, LA 70118 USA

[14] Ottawa Hosp, Res Inst, Dept Med, Ottawa, ON, Canada

[15] Maastricht Univ, Med Ctr, Dept Internal Med, Maastricht, Netherlands

[16] Maastricht Univ, Med Ctr, Sch Cardiovasc Dis CARIM, Maastricht, Netherlands

[17] La Timone Hosp, Lab Haematol, Marseille, France

[18] Aix Marseille Univ, Nutr Obes & Risk Thrombosis, Unite Mixte Rech Sante UMR S 1062, INSERM, Marseille, France

来源：

EPIGENOMICS | 2017年 / 9卷 / 11期

基金：

加拿大健康研究院;

关键词：

450 k array; association; DMP; DMR; DNA methylation; epigenome-wide analysis; homocysteine; meta-analysis; ESTROGEN-RECEPTOR-ALPHA; PLASMA HOMOCYSTEINE; FOLIC-ACID; S-ADENOSYLHOMOCYSTEINE; LIM PROTEIN; LOWERING HOMOCYSTEINE; EPIGENETIC REGULATION; CELL-PROLIFERATION; RISK-FACTOR; FATTY-ACID;

D O I：

10.2217/epi-2017-0038

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Aim: Homocysteine (Hcy) is a sensitive marker of one-carbon metabolism. Higher Hcy levels have been associated with global DNA hypomethylation. We investigated the association between plasma Hcy and epigenome-wide DNA methylation in leukocytes. Methods: Methylation was measured using Illumina 450 k arrays in 2035 individuals from six cohorts. Hcy-associated differentially methylated positions and regions were identified using meta-analysis. Results: Three differentially methylated positions cg21607669 (SLC27A1), cg26382848 (AJUBA) and cg10701000 (KCNMA1) at chromosome 19, 14 and 10, respectively, were significantly associated with Hcy. In addition, we identified 68 Hcy-associated differentially methylated regions, the most significant of which was a 1.8-kb spanning domain (TNXB/ATF6B) at chromosome 6. Conclusion: We identified novel epigenetic loci associated with Hcy levels, of which specific role needs to be further validated.

引用

页码：1403 / 1422

页数：20

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