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

• Published in: Nutrition, metabolism, and cardiovascular diseases Vol. 24; no. 5; pp. 483 - 488
• Main Authors: Fiorito, G., Guarrera, S., Valle, C., Ricceri, F., Russo, A., Grioni, S., Mattiello, A., Di Gaetano, C., Rosa, F., Modica, F., Iacoviello, L., Frasca, G., Tumino, R., Krogh, V., Panico, S., Vineis, P., Sacerdote, C., Matullo, G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2014
• Subjects: 5' untranslated regions; Adult; algorithms; Aminomethyltransferase - genetics; Aryldialkylphosphatase - genetics; B-vitamins; carbon metabolism; Cardiovascular; Case-Control Studies; DNA methylation; DNA Methylation - drug effects; enzymes; Female; females; folic acid; Follow-Up Studies; genes; Homocysteine; Homocysteine - biosynthesis; Humans; Logistic Models; Male; males; Metabolic Networks and Pathways - genetics; Middle Aged; Multivariate Analysis; Myocardial infarction; Myocardial Infarction - epidemiology; Myocardial Infarction - prevention & control; One Carbon Metabolism; Promoter Regions, Genetic; Prospective Studies; regression analysis; Risk Factors; Transcobalamins - genetics; Vitamin B Complex - administration & dosage; Myocardial infarction; WHR; B-vitamins; One Carbon Metabolism; DMR; CVD; OCM; RPMM; DNA-methylation; Homocysteine; CHD; Hcy; BMI; cardiovascular disease; differentially methylated region; waist-hip ratio; body mass index (BMI); recursively partitioned mixture model; coronary heart disease
• ISSN: 0939-4753; 1590-3729; 1590-3729
• DOI: 10.1016/j.numecd.2013.10.026

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. 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. 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.