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

Pooja R. Mandaviya, Dylan Aissi, Koen F. Dekkers, Roby Joehanes, Silva Kasela, Vinh Truong, Lisette Stolk, Diana van Heemst, M. Arfan Ikram, Jan Lindemans, P. Eline Slagboom, David-Alexandre Tregouet, Andre G. Uitterlinden, Chen Wei, Phil Wells, France Gagnon, Marleen M. J. van Greevenbroek, Bastiaan T. Heijmans, Lili Milani, Pierre-Emmanuel MorangeJoyce B. J. van Meurs, Sandra G. Heil*, BIOS Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Web of Science)

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.

Original languageEnglish
Pages (from-to)1403-1422
Number of pages20
JournalEpigenomics
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 2017

Keywords

  • 450 k array
  • association
  • DMP
  • DMR
  • DNA methylation
  • epigenome-wide analysis
  • homocysteine
  • meta-analysis
  • RANDOMIZED CONTROLLED-TRIAL
  • ESTROGEN-RECEPTOR-ALPHA
  • SMOOTH-MUSCLE-CELLS
  • PLASMA HOMOCYSTEINE
  • S-ADENOSYLHOMOCYSTEINE
  • GENOME-WIDE
  • FOLIC-ACID
  • VASCULAR-DISEASE
  • LIM PROTEIN
  • MYOCARDIAL-INFARCTION

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