Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China.
Gynecology & Obstetrics Department, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, China.
J Clin Lab Anal. 2020 Aug;34(8):e23322. doi: 10.1002/jcla.23322. Epub 2020 Apr 22.
DHFR encodes dihydrofolate reductase, a major enzyme in the metabolism of folate, and is a candidate gene for ischemic stroke (IS). Therefore, we aimed to investigate the association between DHFR promoter methylation and IS in a Chinese population with primary hypertension.
Quantitative methylation-specific PCR was used to measure the level of DHFR promoter methylation. A multivariate logistic regression model was used to investigate the association between DHFR promoter methylation and IS. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of DHFR promoter methylation for IS.
The level of methylation of the DHFR promoter in the IS group was significantly lower than that in the hypertensive group (median [interquartile range]: 9.11 [2.81-16.20] vs 24.94 [7.16-56.45], P < .001). DHFR promoter methylation and homocysteine (Hcy) levels were both related to IS, with an ORs (95% CI) of 0.976 (0.967-0.984) and 1.057 (1.027-1.108), respectively. The areas under the curve for the diagnosis of DHFR promoter hypomethylation in IS were 0.603 (95% CI, 0.527-0.678) in men and 0.754 (95% CI, 0.693-0.815) in women. A dual-luciferase reporter assay revealed that the target sequence in the DHFR promoter upregulated gene expression.
There is a significant association between methylation of the DHFR promoter and IS in this Chinese hypertensive population. Hypomethylation of the DHFR promoter may serve as a novel marker for the diagnosis of IS in women.
DHFR 编码二氢叶酸还原酶，是叶酸代谢中的一种主要酶，也是缺血性中风（IS）的候选基因。因此，我们旨在研究中国原发性高血压人群中 DHFR 启动子甲基化与 IS 之间的关系。
采用定量甲基化特异性 PCR 测量 DHFR 启动子甲基化水平。采用多变量逻辑回归模型研究 DHFR 启动子甲基化与 IS 之间的关系。采用受试者工作特征（ROC）曲线分析评估 DHFR 启动子甲基化对 IS 的诊断价值。
IS 组 DHFR 启动子的甲基化水平明显低于高血压组（中位数[四分位距]：9.11[2.81-16.20] 比 24.94[7.16-56.45]，P<0.001）。DHFR 启动子甲基化和同型半胱氨酸（Hcy）水平均与 IS 相关，OR（95%CI）分别为 0.976（0.967-0.984）和 1.057（1.027-1.108）。DHFR 启动子低甲基化诊断 IS 的曲线下面积在男性中为 0.603（95%CI，0.527-0.678），在女性中为 0.754（95%CI，0.693-0.815）。双荧光素酶报告基因检测显示，DHFR 启动子的靶序列上调了基因表达。
在中国高血压人群中，DHFR 启动子甲基化与 IS 之间存在显著关联。DHFR 启动子低甲基化可能成为女性 IS 诊断的新标志物。
