B-vitamins intake, DNA-methylation of One Carbon Metabolism and homocysteine pathway genes and myocardial infarction risk: The EPICOR study
B-vitamins intake, DNA-methylation of One Carbon Metabolism and homocysteine pathway genes and myocardial infarction risk: The EPICOR study
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DOI：
10.1016/j.numecd.2013.10.026
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发表时间：
2014-05-01
影响因子：
3.9
通讯作者：
Matullo, G.
中科院分区：
文献类型：
--
作者：
Fiorito, G.;Guarrera, S.;Matullo, G.
背景和目标：一些流行病学研究强调了叶酸和B族维生素摄入量低与心血管疾病风险之间的关系。报道了叶酸摄入量与DNA甲基化之间关系的对比结果。叶酸和B族维生素可以调节特定酶的DNA甲基化，这些酶包括在一碳代谢（OCM）和同型半胱氨酸（Hcy）途径中。本研究的目的是评估是否DNA甲基化的档案OCM和Hcy基因可以调节心肌梗死（MI）的风险所赋予的低B族维生素intake.Methods和results：研究样本（206 MI病例和206匹配对照）是一个病例对照研究嵌套在前瞻性EPIC队列。通过全表观基因组分析（Illumina-HumanMethylation 450 K-BeadChip）提取33个候选基因的甲基化水平。我们在男性中鉴定了三个差异甲基化区域（TCN 2启动子，CBS 5 'UTR，AMT基因体），在女性中鉴定了两个差异甲基化区域（PON 1基因体，CBS 5' UTR），每个区域的特征在于在病例中甲基化增加。功能性计算机模拟分析表明，在病例中表达降低。递归分区混合模型聚类算法识别了与不同MI风险相关的不同甲基化谱：男性和女性中高风险与低风险甲基化谱组，OR = 3.49，p = 1.87 x 10（-4）和OR = 3.94，p = 0.0317（针对经典CVD风险因素调整的多变量logistic回归）。此外，一般的B族维生素摄入量和候选基因的DNA甲基化之间呈反比关系observed.Conclusions：我们的研究结果支持的假设，即DNA甲基化模式在特定区域的OCM和Hcy途径基因可能调节叶酸和B族维生素低摄入量所赋予的CVD风险。(C)2013爱思唯尔有限公司版权所有。
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 x 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. (C) 2013 Elsevier B.V. All rights reserved.