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. 2014 May;24(5):483-8.
doi: 10.1016/j.numecd.2013.10.026. Epub 2013 Nov 6.

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

G Fiorito  1 , S Guarrera  2 , C Valle  2 , F Ricceri  1 , A Russo  1 , S Grioni  3 , A Mattiello  4 , C Di Gaetano  1 , F Rosa  2 , F Modica  2 , L Iacoviello  5 , G Frasca  6 , R Tumino  6 , V Krogh  3 , S Panico  4 , P Vineis  7 , C Sacerdote  8 , G Matullo  9
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Free article

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

G Fiorito et al. Nutr Metab Cardiovasc Dis. 2014 May.
Free article

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.

Keywords: B-vitamins; DNA-methylation; Homocysteine; Myocardial infarction; One Carbon Metabolism.

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