Nanshan Center for Chronic Disease Control, Shenzhen, China.
Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong, China.
Bosn J Basic Med Sci. 2020 Nov 2;20(4):477-486. doi: 10.17305/bjbms.2020.4636.
The MTHFR gene encodes methylenetetrahydrofolate reductase required for the metabolism of homocysteine (Hcy) - a previously reported independent risk factor for ischemic stroke (IS). In this study, we first aimed to clarify the association between DNA methylation levels in the MTHFR promoter and the risk of IS, followed by the analysis of potential interactions between environmental factors and DNA methylation levels that affect IS risk. We recruited 164 patients with hypertension and IS (case group) and 345 age-matched and sex-matched patients with hypertension only (control group). Demographic and clinical information was obtained using questionnaires, and blood samples were collected for biochemical analyses. Fluorescence quantitative methylation-specific PCR (qMSP) was used to detect MTHFR promoter methylation levels. A logistic regression analysis was performed to determine the relationship between environmental factors, MTHFR promoter methylation levels, and IS risk. We finally generated a receiver operating characteristic curve to determine whether MTHFR promoter methylation levels can predict IS. The mean MTHFR methylation levels in the case group (8.10 ± 6.14) were significantly lower than those in the control group (17.44 ± 3.16; p < 0.05). MTHFR promoter methylation levels were also lower in patients with plasma Hcy levels ≥15 μmol/L (10.65 ± 4.05) than in those with Hcy levels <15 μmol/L (16.74 ± 4.26, p < 0.001). Finally, we found that MTHFR hypermethylation is a protective factor for IS, particular in men (OR in men: 0.07; 95% CI: 0.02-0.16; p < 0.001). Further, sex and MTHFR promoter methylation levels exhibited a preliminary interaction effect on IS risk. These results indicate that MTHFR promoter methylation status might have diagnostic value in IS.
亚甲基四氢叶酸还原酶（MTHFR）基因编码同型半胱氨酸（Hcy）代谢所必需的亚甲基四氢叶酸还原酶，Hcy 是缺血性脑卒中（IS）的独立危险因素。本研究旨在阐明 MTHFR 启动子 DNA 甲基化水平与 IS 风险的关系，分析环境因素与 DNA 甲基化水平之间的潜在相互作用对 IS 风险的影响。我们招募了 164 例高血压合并 IS 患者（病例组）和 345 例年龄和性别匹配的单纯高血压患者（对照组）。采用问卷调查收集人口统计学和临床信息，采集血样进行生化分析。采用荧光定量甲基化特异性 PCR（qMSP）检测 MTHFR 启动子甲基化水平。采用 logistic 回归分析环境因素、MTHFR 启动子甲基化水平与 IS 风险的关系。最后，我们生成受试者工作特征曲线，以确定 MTHFR 启动子甲基化水平是否可以预测 IS。病例组的平均 MTHFR 甲基化水平（8.10±6.14）显著低于对照组（17.44±3.16；p<0.05）。血浆 Hcy 水平≥15μmol/L 的患者的 MTHFR 启动子甲基化水平（10.65±4.05）也低于 Hcy 水平<15μmol/L 的患者（16.74±4.26，p<0.001）。最后，我们发现 MTHFR 高甲基化是 IS 的保护因素，尤其是男性（男性 OR：0.07；95%CI：0.02-0.16；p<0.001）。此外，性别和 MTHFR 启动子甲基化水平对 IS 风险具有初步的交互作用。这些结果表明，MTHFR 启动子甲基化状态可能对 IS 具有诊断价值。
