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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)483-488
Number of pages6
JournalNutrition, Metabolism and Cardiovascular Diseases
Issue number5
Publication statusPublished - 2014


  • B-vitamins
  • DNA-methylation
  • Homocysteine
  • Myocardial infarction
  • One carbon metabolism

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)


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