| Institution: | 1. Discipline of Medical Biochemistry and Chemical Pathology, Howard College Campus, University of KwaZulu-Natal, Durban, South Africa;2. Department of Physiology, School of Medicine, Faculty of Health Sciences, Prinshof Campus, University of Pretoria, South Africa;3. Department of Cardiology, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa;2. Institute for Molecular and Cell Biology (IBMC), Universidade do Porto, Porto, Portugal;3. Department of Urology, Central Hospital of S. João, Porto, Portugal;4. Requimte/Department of Chemistry & Biochemistry, Faculty of Sciences, Universidade do Porto, Porto, Portugal;5. Faculty of Nutrition and Food Sciences, Universidade do Porto, Porto, Portugal;1. Centre of Excellence for Nutrition (CEN), North-West University, Potchefstroom Campus, South Africa;2. Statistical Consultation Service, North-West University, Potchefstroom Campus, South Africa;3. Physical Activity, Sport and Recreation (PhASRec), School of Biokinetics, Recreation and Sport Science, North-West University, Potchefstroom Campus, South Africa;4. Division of Human Nutrition, Wageningen University, The Netherlands |
| Abstract: | Background and aimsSeveral epidemiological studies highlighted the association between folate and B-vitamins low intake and cardiovascular diseases (CVD) risk. Contrasting results were reported on the relationship between folate intake and DNA-methylation. Folate and B-vitamins may modulate DNA-methylation of specific enzymes which are included in the One-Carbon Metabolism (OCM) and in the homocysteine (Hcy) pathways. The aim of the study was to evaluate whether DNA-methylation profiles of OCM and Hcy genes could modulate the myocardial infarction (MI) risk conferred by a low B-vitamins intake.Methods and resultsStudy sample (206 MI cases and 206 matched controls) is a case-control study nested in the prospective EPIC cohort. Methylation levels of 33 candidate genes where extracted by the whole epigenome analysis (Illumina-HumanMethylation450K-BeadChip). We identified three differentially methylated regions in males (TCN2 promoter, CBS 5′UTR, AMT gene-body) and two in females (PON1 gene-body, CBS 5′UTR), each of them characterized by an increased methylation in cases. Functional in silico analysis suggested a decreased expression in cases. A Recursively Partitioned Mixture Model cluster algorithm identified distinct methylation profiles associated to different MI risk: high-risk vs. low-risk methylation profile groups, OR = 3.49, p = 1.87 × 10?4 and OR = 3.94, p = 0.0317 in males and females respectively (multivariate logistic regression adjusted for classical CVD risk factors). Moreover, a general inverse relationship between B-vitamins intake and DNA-methylation of the candidate genes was observed.ConclusionsOur findings support the hypothesis that DNA-methylation patterns in specific regions of OCM and Hcy pathways genes may modulate the CVD risk conferred by folate and B-vitamins low intake. |
