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Homocysteine levels associate with subtle changes in leukocyte DNA methylation: an epigenome-wide analysis
Pooja R Mandaviya1,2, Dylan Aïssi3,4, Koen F Dekkers5
1Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.
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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