Zhang Huan, Mo Xingbo, Wang Aili, Peng Hao, Guo Daoxia, Zhong Chongke, Zhu Zhengbao, Xu Tan, Zhang Yonghong
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China.
Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China.
Front Cardiovasc Med. 2022 Mar 8;9:796245. doi: 10.3389/fcvm.2022.796245. eCollection 2022.
A genome-wide association study identified 12 genetic loci influencing blood pressure and implicated a role of DNA methylation. However, the relationship between methylation and ischemic stroke has not yet been clarified. We conducted a large-sample sequencing study to identify blood leukocyte DNA methylations as novel biomarkers for ischemic stroke risk and prognosis based on previously identified genetic loci.
Methylation levels of 17 genes were measured by sequencing in 271 ischemic stroke cases and 323 controls, and the significant associations were validated in another independent sample of 852 cases and 925 controls. The associations between methylation levels and ischemic stroke risk and prognosis were evaluated.
Methylation of and was significantly associated with ischemic stroke. Compared to participants without any hypomethylated targets, the odds ratio (OR) (95% confidence interval, CI) for those with 9 hypomethylated genes was 1.41 (1.33-1.51) for ischemic stroke. Adding methylation levels of the 9 genes to the basic model of traditional risk factors significantly improved the risk stratification for ischemic stroke. Associations between and gene methylation and modified Rankin Scale scores were significant after adjustment for covariates. Lower methylation levels of and were significantly associated with increased 3-month mortality. Compared to patients without any hypomethylated targets, the OR (95% CI) for those with 4 hypomethylated targets was 1.12 (1.08-1.15) for 3-month mortality ( = 2.28 × 10).
The present study identified blood leukocyte DNA methylations as potential factors affecting ischemic stroke risk and prognosis among Han Chinese individuals.
一项全基因组关联研究确定了12个影响血压的基因位点，并暗示了DNA甲基化的作用。然而，甲基化与缺血性中风之间的关系尚未阐明。我们基于先前确定的基因位点进行了一项大样本测序研究，以确定血液白细胞DNA甲基化作为缺血性中风风险和预后的新型生物标志物。
通过测序测量了271例缺血性中风病例和323例对照中17个基因的甲基化水平，并在另一个由852例病例和925例对照组成的独立样本中验证了显著关联。评估了甲基化水平与缺血性中风风险和预后之间的关联。
[基因名称1]和[基因名称2]的甲基化与缺血性中风显著相关。与没有任何低甲基化靶点的参与者相比，具有9个低甲基化基因的参与者发生缺血性中风的比值比（OR）（95%置信区间，CI）为1.41（1.33 - 1.51）。将这9个基因的甲基化水平添加到传统危险因素的基本模型中，显著改善了缺血性中风的风险分层。在调整协变量后，[基因名称1]和[基因名称2]基因甲基化与改良Rankin量表评分之间的关联显著。[基因名称1]和[基因名称2]较低的甲基化水平与3个月死亡率增加显著相关。与没有任何低甲基化靶点的患者相比，具有4个低甲基化靶点的患者3个月死亡率的OR（95%CI）为1.12（1.08 - 1.15）（P = 2.28×10）。
本研究确定血液白细胞DNA甲基化是影响汉族个体缺血性中风风险和预后的潜在因素。
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