Homocysteine levels associate with subtle changes in leukocyte DNA methylation: an epigenome-wide analysis. (November 2017)

• Record Type: Journal Article
• Authors: Mandaviya, Pooja R; Aïssi, Dylan; Dekkers, Koen F; Joehanes, Roby; Kasela, Silva; Truong, Vinh; Stolk, Lisette; Heemst, Diana van; Ikram, M Arfan; Lindemans, Jan; Slagboom, P Eline; Trégouët, David-Alexandre; Uitterlinden, André G; Wei, Chen; Wells, Phil; Gagnon, France; van Greevenbroek, Marleen MJ; Heijmans, Bastiaan T; Milani, Lili; Morange, Pierre-Emmanuel; van Meurs, Joyce BJ; Heil, Sandra G
• Is Part Of: Epigenomics. Volume 9:Number 11(2017)
• Page Start: 1403
• Page End: 1422
• Publication Date: 2017-11
• Subjects: 450 k array -- association -- DMP -- DMR -- DNA methylation -- epigenome-wide analysis -- homocysteine -- meta-analysis; Epigenesis -- Periodicals; Genomics -- Periodicals; Chromatin -- Periodicals; DNA -- Periodicals; 572.87
• DOI: 10.2217/epi-2017-0038
• Languages: English
• ISSNs: 1750-1911

Abstract

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.