Common Polymorphisms in the RGMa Promoter Are Associated With Cerebrovascular Atherosclerosis Burden in Chinese Han Patients With Acute Ischemic Cerebrovascular Accident

作者：Qingzhe Hu, Zhenlei Chen, Xiaofan Yuan, Shucheng Li, Rongrong Zhang, Xinyue Qin · 发表于：Frontiers in Cardiovascular Medicine · 年份：2021 · DOI：10.3389/fcvm.2021.743868 · 被引用次数：6 · 研究领域：Blood Coagulation and Thrombosis Mechanisms、Axon Guidance and Neuronal Signaling、Cardiovascular, Neuropeptides, and Oxidative Stress Research

Repulsive guidance molecule a (RGMa) plays a vital role in the progression of numerous inflammatory diseases. However, whether it participates in atherosclerosis development is not known. Here, we explored the influence of RGMa in atherogenesis by investigating whether an association exists between functional polymorphisms in the RGMa promoter and cerebrovascular atherosclerosis burden (CAB) in Chinese Han patients diagnosed with acute ischemic cerebrovascular accident. To this end, we conducted a genetic association study on 201 patients with prior diagnoses of acute ischemic stroke or transient ischemic attack recruited from our hospital. After admission, we conducted three targeted single-nucleotide polymorphisms (SNPs) genotyping and evaluated CAB by computed tomography angiography. We used logistic regression modeling to analyze genetic associations. Functional polymorphism analysis indicated an independent association between the rs725458 T allele and increased CAB in patients with acute ischemic cerebrovascular accident [adjusted odds ratio (OR) = 1.66, 95% confidence interval (CI) = 1.01–2.74, P = 0.046]. In contrast, an association between the rs4778099 AA genotype and decreased CAB (adjusted OR = 0.10, 95% CI = 0.01–0.77, P = 0.027) was found. Our Gene Expression Omnibus analysis revealed lower RGMa levels in the atherosclerotic aortas and in the macrophages isolated from plaques than that in the normal aortas and macrophages from normal tissue, respectively. In con...