Dysregulation of the oxidant-antioxidant system contributes to the pathogenesis of cerebral stroke (CS). Epigenetic changes of redox homeostasis genes, such as glutamate-cysteine ligase (GCLM), glutathione-S-transferase-P1 (GSTP1), thioredoxin reductase 1 (TXNRD1), and myeloperoxidase (MPO), may be biomarkers of CS. In this study, we assessed the association of DNA methylation levels of these genes with CS and clinical features of CS. We quantitatively analyzed DNA methylation patterns in the promoter or regulatory regions of 4 genes (GCLM, GSTP1, TXNRD1, and MPO) in peripheral blood leukocytes of 59 patients with CS in the acute phase and in 83 relatively healthy individuals (controls) without cardiovascular and cerebrovascular diseases. We found that in both groups, the methylation level of CpG sites in genes TXNRD1 and GSTP1 was ≤ 5%. Lower methylation levels were registered at a CpG site (chr1:94,374,293, GRCh37 [hg19]) in GCLM in patients with ischemic stroke compared with the control group (9% [7%; 11.6%] (median and interquartile range) versus 14.7% [10.4%; 23%], respectively, p < 0.05). In the leukocytes of patients with CS, the methylation level of CpG sites in the analyzed region of MPO (chr17:56,356,470, GRCh3 [hg19]) on average was significantly lower (23.5% [19.3%; 26.7%]) than that in the control group (35.6% [30.4%; 42.6%], p < 0.05). We also found increased methylation of MPO in smokers with CS (27.2% [23.5%; 31.1%]) compared with nonsmokers with CS (21.7% [18.1%; 24.8%]). Thus, hypomethylation of CpG sites in GCLM and MPO in blood leukocytes is associated with CS in the acute phase.

氧化 - 抗氧化系统的失调有助于脑卒中 (CS) 的发病机制。谷氨酸-半胱氨酸连接酶（ GCLM）、谷胱甘肽-S-转移酶-P1（GSTP1）、硫氧还蛋白还原酶1（TXNRD1）和髓过氧化物酶（MPO ）等氧化还原稳态基因的表观遗传变化可能是CS的生物标志物。在这项研究中，我们评估了这些基因的 DNA 甲基化水平与 CS 和 CS 临床特征的关联。我们定量分析了 4 个基因（ GCLM、GSTP1、TXNRD1和MPO）的启动子或调控区域的 DNA 甲基化模式。) 在 59 名急性期 CS 患者和 83 名没有心脑血管疾病的相对健康个体（对照）的外周血白细胞中。我们发现，在两组中，基因TXNRD1和GSTP1中CpG位点的甲基化水平≤5%。与对照组相比，缺血性卒中患者GCLM 的 CpG 位点（chr1:94,374,293，GRCh37 [hg19]）甲基化水平低于对照组（9% [7%; 11.6%]（中位数和四分位间距）对 14.7% [10.4%; 23%]，分别，p  < 0.05）。在 CS 患者的白细胞中， MPO分析区域中 CpG 位点的甲基化水平(chr17:56,356,470, GRCh3 [hg19]) 平均显着低于对照组 (23.5% [19.3%; 26.7%]) (35.6% [30.4%; 42.6%], p  < 0.05)。我们还发现，与患有 CS 的非吸烟者（21.7% [18.1%；24.8%]）相比，患有 CS 的吸烟者（27.2% [23.5%; 31.1%]）的MPO甲基化增加。因此，GCLM 中 CpG 位点的低甲基化和血液白细胞中MPO与急性期的 CS 相关。