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

Pooja R Mandaviya, Dylan Aïssi, Koen F Dekkers, Roby Joehanes, Silva Kasela, Vinh Truong, Lisette Stolk, Diana van Heemst, M Arfan Ikram, Jan Lindemans, P Eline Slagboom, David-Alexandre Trégouët, André G Uitterlinden, Chen Wei, Phil Wells, France Gagnon, Marleen Mj van Greevenbroek, Bastiaan T Heijmans, Lili Milani, Pierre-Emmanuel Morange, Joyce Bj van Meurs, Sandra G Heil
Epigenomics 2017 November
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.

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