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首页> 外文期刊>Clinical epigenetics. >Vitamin and antioxidant rich diet increases MLH1 promoter DNA methylation in DMT2 subjects
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Vitamin and antioxidant rich diet increases MLH1 promoter DNA methylation in DMT2 subjects

机译：富含维生素和抗氧化剂的饮食可增加DMT2受试者MLH1启动子DNA甲基化

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BackgroundOxidative stress may lead to an increased level of unrepaired cellular DNA damage, which is discussed as one risk for tumor initiation. Mismatch repair (MMR) enzymes act as proofreading complexes that maintain the genomic integrity and MMR-deficient cells show an increased mutation rate. One important gene in the MMR complex is the MutL homolog 1 ( MLH1 ) gene. Since a diet rich in antioxidants has the potential to counteract harmful effects by reactive oxygen species (ROS), we investigated the impact of an antioxidant, folate, and vitamin rich diet on the epigenetic pattern of MLH1 . These effects were analyzed in individuals with non-insulin depended diabetes mellitus type 2 (NIDDM2) and impaired fasting glucose (IFG). MethodsIn this post-hoc analysis of a randomized trial we analyzed DNA methylation of MLH1 , MSH2 , and MGMT at baseline and after 8 weeks of intervention, consisting of 300 g vegetables and 25 ml plant oil rich in polyunsaturated fatty acids per day. DNA methylation was quantified using combined bisulfite restriction enzyme analysis (COBRA) and pyrosequencing. MLH1 and DNMT1 mRNA expression were investigated by qRT-PCR. DNA damage was assessed by COMET assay. Student’s two-tailed paired t test and one-way ANOVA with Scheffé corrected Post hoc test was used to determine significant methylation and expression differences. Two-tailed Pearson test was used to determine correlations between methylation level, gene expression, and DNA strand break amount. ResultsThe intervention resulted in significantly higher CpG methylation in two particular MLH1 promoter regions and the MGMT promoter. DNA strand breaks and methylation levels correlated significantly. The expression of MLH1 , DNMT1 , and the promoter methylation of MSH2 remained stable. CpG methylation levels and gene expression did not correlate. ConclusionThis vitamin and antioxidant rich diet affected the CpG methylation of MLH1 . The higher methylation might be a result of the ROS scavenging antioxidant rich diet, leading to lower activity of DNA demethylating enzymes. Our results suggest the hypothesis of CpG demethylation via DNA repair enzymes under these circumstances. NIDDM2 and IFG patients benefit from this simple dietary intervention involving epigenetic and DNA repair mechanisms.
机译：背景氧化应激可能导致未修复的细胞DNA损伤水平升高，这被认为是引发肿瘤的一种风险。错配修复（MMR）酶充当校对复合体，可维持基因组完整性，而MMR缺陷型细胞显示出更高的突变率。 MMR复合物中的一个重要基因是MutL同系物1（MLH1）基因。由于富含抗氧化剂的饮食具有抵消活性氧（ROS）有害影响的潜力，因此我们研究了富含抗氧化剂，叶酸和维生素的饮食对MLH1后生模式的影响。在患有非胰岛素依赖型2型糖尿病（NIDDM2）和空腹血糖受损（IFG）的个体中分析了这些作用。方法在这项随机试验的事后分析中，我们分析了基线和干预后8周后MLH1，MSH2和MGMT的DNA甲基化情况，其中包括每天300克蔬菜和25毫升富含多不饱和脂肪酸的植物油。结合使用亚硫酸氢盐限制酶分析（COBRA）和焦磷酸测序对DNA甲基化进行定量。通过qRT-PCR研究MLH1和DNMT1mRNA的表达。通过COMET分析评估DNA损伤。使用学生的两尾配对t检验和经过Scheffé校正的Post hoc检验的单向方差分析来确定明显的甲基化和表达差异。使用两尾皮尔逊检验确定甲基化水平，基因表达和DNA链断裂量之间的相关性。结果干预导致在两个特定的MLH1启动子区域和MGMT启动子中CpG甲基化显着提高。 DNA链断裂和甲基化水平显着相关。 MLH1，DNMT1的表达和MSH2的启动子甲基化保持稳定。 CpG甲基化水平与基因表达不相关。结论富含维生素和抗氧化剂的饮食影响MLH1的CpG甲基化。较高的甲基化可能是由于ROS清除了富含抗氧化剂的饮食，导致DNA脱甲基酶的活性降低。我们的结果表明在这种情况下通过DNA修复酶进行CpG去甲基化的假说。 NIDDM2和IFG患者可从涉及表观遗传和DNA修复机制的简单饮食干预中受益。

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