N6-甲基腺苷甲基化与老年急性心肌梗死的相关性研究

Correlation between N6-methyladenosine methylation and acute myocardial infarction in elderly patients

目的探讨N6-甲基腺苷(m6A)甲基化与老年急性心肌梗死(AMI)的相关性。方法收集新疆医科大学第五附属医院2016年12月至2022年9月收治的老年AMI患者108例(观察组)及同期住院体检的102例无心血管疾病老年人(对照组)的临床资料行回顾性分析。对比2组一般资料及血生化指标。比色法测定2组外周血单个核细胞总RNA的m6A水平进行比较,实时荧光定量聚合酶链反应及蛋白质免疫印迹法检测2组m6A修饰相关酶甲基转移酶[甲基化转移酶3(METTL3)、METTL14、肾母细胞瘤1关联蛋白(WTAP)]和去甲基转移酶[肥胖相关蛋白(FTO)、烷烃羟化酶同源5基因(ALKBH5)]mRNA及蛋白相对表达量的差异,分析其与老年AMI的相关性。结果观察组体重指数、糖尿病史比例、空腹血糖及低密度脂蛋白胆固醇水平显著高于对照组(均P<0.05)。观察组外周血单个核细胞总RNA的m6A水平显著高于对照组[(0.56±0.03)比(0.48±0.28)],差异有统计学意义(P<0.001)。二元Logistic回归分析结果显示m6A为老年AMI的危险因素(比值比=4.338,95%置信区间:1.571~11.975,P=0.005),m6A水平预测老年AMI的曲线下面积为0.982,敏感度为91.11%,特异度为95.56%。观察组METTL3、METTL14 mRNA和蛋白相对表达量显著高于对照组,WTAP、FTO及ALKBH5 mRNA和蛋白相对表达量显著低于对照组,差异均有统计学意义(均P<0.001)。结论m6A为老年AMI的危险因素,m6A对老年心肌梗死具有一定的预测价值;m6A甲基化与老年AMI存在相关性,老年AMI患者METTL3与METTL14表达量高,WTAP、FTO与ALKBH5的表达量低,m6A及其修饰相关酶有望为老年AMI患者诊治提供潜在新视角。

Objective To analyze the correlation between N6-methyladenosine(m6A)methylation and acute myocardial infarction(AMI)in elderly patients.Methods The clinical data of 108 elderly AMI patients(observation group)admitted to the Fifth Affiliated Hospital of Xinjiang Medical University from December 2016 to September 2022 and 102 elderly patients without cardiovascular disease(control group)admitted to the hospital at the same time were collected for retrospective analysis.The general data and blood biochemical indicators of the two groups were compared.The level of m6A of total RNA in peripheral blood mononuclear cell measured by colorimetry was compared between the two groups;real-time quantitative fluorescence polymerase chain reaction and western blot were used to detect the difference of mRNA and protein relative expression of m6A modification related enzymes methyltransferase[methyltransferase 3(METTL3),METTL14,Wilms′tumor 1 associated protein(WTAP)]and demethylation transferase[fat mass and obesity associated protein(FTO),alkane hydroxylase homologous 5 gene(ALKBH5)]in the two groups,and the correlation of them with elderly AMI was analyzed.Results The body mass index,the proportion of diabetes mellitus history,the levels of fasting blood glucose and low-density lipoprotein cholesterol in the observation group were significantly higher than those in the control group(all P<0.05).The total RNA m6A level of peripheral blood mononuclear cell in the observation group was significantly higher than that in the control group[(0.56±0.03)vs(0.48±0.28)](P<0.001).Binary Logistic regression analysis showed that m6A was a risk factor for elderly AMI(odds ratio=4.338,95%confidence interval:1.571-11.975,P=0.005);the area under the curve for m6A level in predicting elderly AMI was 0.982,with a sensitivity of 91.11%and a specificity of 95.56%.The relative expression levels of METTL3 and METTL14 mRNA and protein in the observation group were significantly higher than those in the control group,while the relative expression levels of WTAP,FTO,and ALKBH5 mRNA and protein were significantly lower than those in the control group(all P<0.001).Conclusions m6A is a risk factor and has certain predicted value for AMI in the elderly.m6A methylation is associated with AMI in the elderly.The expression levels of METTL3 and METTL14 are high in elderly AMI patients,while the expression levels of WTAP,FTO and ALKBH5 are low.m6A and its modification related enzymes are expected to provide a potential new perspective for the diagnosis and treatment of elderly AMI patients.