Association of DNA Methylation in Blood Pressure-Related Genes With Ischemic Stroke Risk and Prognosis

Frontiers in Cardiovascular Medicine

article

Xingbo Mo¹  Aili Wang¹  Hao Peng¹  Daoxia Guo¹  Chongke Zhong¹  Zhengbao Zhu¹  Tan Xu¹  Yonghong Zhang¹  Huan Zhang¹ 

[1] Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University;Department of Epidemiology, School of Public Health, Medical College of Soochow University;Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University

关键词: prognosis;    methylation;    stroke;    blood pressure;    mortality;   

DOI  :  10.3389/fcvm.2022.796245

学科分类：地球科学(综合)

来源: Frontiers

【 摘 要 】

Background 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. Methods 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. Results Methylation of AMH, C17orf82, HDAC9, IGFBP3, LRRC10B, PDE3A, PRDM6, SYT7 and TBX2 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 AMH, HDAC9, IGFBP3, PDE3A and PRDM6 gene methylation and modified Rankin Scale scores were significant after adjustment for covariates. Lower methylation levels of AMH, C17orf82, PRDM6 and TBX2 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 ( P = 2.28 × 10 −10 ). Conclusion The present study identified blood leukocyte DNA methylations as potential factors affecting ischemic stroke risk and prognosis among Han Chinese individuals.

【 授权许可】

CC BY