B-vitamins intake, DNA-methylation of One Carbon Metabolism and homocysteine pathway genes and myocardial infarction risk: the EPICOR study.

G Fiorito, S Guarrera, C Valle, F Ricceri, A Russo, S Grioni, A Mattiello, C Di Gaetano, F Rosa, F Modica, L Iacoviello, G Frasca, R Tumino, V Krogh, S Panico, P Vineis, C Sacerdote, G Matullo

Journal: Nutrition, metabolism, and cardiovascular diseases : NMCD 2014;24(5):483-8

PMID: 24418380

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Abstract

BACKGROUND AND AIMS

Several 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 RESULTS

Study 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.

CONCLUSIONS

Our 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.

Address: Human Genetics Foundation, Torino, Italy; Department of Medical Sciences, University of Torino, Italy.; Human Genetics Foundation, Torino, Italy.; Department of Preventive and Predictive Medicine, Epidemiology and Prevention Unit, Fondazione IRCSS Istituto Nazionale dei Tumori, Milano, Italy.; Department of Clinical and Experimental Medicine, Federico II University, Napoli, Italy.; Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, Italy.; Cancer Registry and Histopathology Unit, "Civile-M.P. Arezzo" Hospital, Ragusa, Italy.; Human Genetics Foundation, Torino, Italy; Epidemiology and Public Health, Imperial College London, UK.; Human Genetics Foundation, Torino, Italy; Cancer Epidemiology, CPO-Piemonte, Torino, Italy.; Human Genetics Foundation, Torino, Italy; Department of Medical Sciences, University of Torino, Italy. Electronic address: [email protected].

DOI: 10.1016/j.numecd.2013.10.026