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

Author:

Mandaviya Pooja R12,Aïssi Dylan34,Dekkers Koen F5,Joehanes Roby6,Kasela Silva78,Truong Vinh9,Stolk Lisette2,Heemst Diana van10,Ikram M Arfan11,Lindemans Jan1,Slagboom P Eline5,Trégouët David-Alexandre34,Uitterlinden André G2,Wei Chen12,Wells Phil13,Gagnon France9,van Greevenbroek Marleen MJ14,Heijmans Bastiaan T5,Milani Lili7,Morange Pierre-Emmanuel1516,van Meurs Joyce BJ2,Heil Sandra G1,

Affiliation:

1. Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands

2. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands

3. Sorbonne Universités, UPMC Univ. Paris 06, INSERM, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris, France

4. ICAN Institute for Cardiometabolism & Nutrition, Paris, France

5. Molecular Epidemiology Section, Department of Medical Statistics & Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands

6. Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School, Boston, MA, USA

7. Estonian Genome Center, University of Tartu, Tartu, Estonia

8. Institute of Molecular & Cell Biology, University of Tartu, Tartu, Estonia

9. Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada

10. Department of Gerontology & Geriatrics Section, Leiden University Medical Center, Leiden, The Netherlands

11. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands

12. Department of Epidemiology, Tulane University, New Orleans, LA, USA

13. Department of Medicine, Ottawa Hospital Research Institute, Ottawa, Canada

14. Department of Internal Medicine & School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands

15. Laboratory of Haematology, La Timone Hospital, Marseille, France

16. Institut National pour la Santé et la Recherche Médicale (INSERM), Unité Mixte de Recherche en Santé (UMR_S) 1062, Nutrition Obesity & Risk of Thrombosis, Aix-Marseille University, Marseille, France

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.

Publisher

Future Medicine Ltd

Subject

Cancer Research,Genetics

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