中风高危人群中与炎症和内皮功能相关的基因多态性、颈动脉粥样硬化和血管事件

Hong Chen, Ting Qing, Hua Luo, Ming Yu, Yanfen Wang, Wei Wei, Yong Xie, Xingyang Yi
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摘要

本研究是在中国西南部四川省开展的一项基于社区的多中心横断面调查和前瞻性队列研究。本研究在四川西南部地区开展了一项多中心社区横断面调查和前瞻性队列研究,随机选取了八个社区,采用结构化面对面问卷调查的方式对每个社区的居民进行了调查。在 2,893 名脑卒中高危人群中,有 2,377 人接受了颈动脉超声检查并获得了 DNA 信息。测量了涉及炎症和内皮功能基因的 19 个 SNPs 的基因型。在面对面调查后,对所有 2377 名受试者进行了长达 4.7 年的随访。在 2377 名受试者中,2205 人(92.8%)完成了 4.7 年的随访,947 人(42.9%)患有颈动脉粥样硬化[372 人(16.9%)患有颈动脉易损斑块,405 人(18.4%)平均 IMT > 0.9 mm,285 人(12.0%)颈动脉狭窄≥15%]。随访期间,158 名(7.2%)受试者出现了预后[92 名(4.2%)缺血性卒中、17 名(0.8%)出血性卒中、48 名(2.2%)心肌梗死和 26 名(1.2%)死亡]。在 19 个 SNPs 中,ITGA2 rs1991013、IL1A rs1609682 和 HABP2 rs7923349 之间存在明显的基因-基因交互作用。多变量逻辑回归模型显示,颈动脉粥样硬化和三个 SNPs 中的高危交互基因型与缺血性脑卒中的较高风险是独立的(OR = 2.67,95% CI:1.52-6.78,P = 0.004;OR = 3.11,95% CI:2.12-9.27, p < 0.001, respectively)和复合血管事件(OR = 3.04, 95% CI: 1.46-6.35, p < 0.001; and OR = 3.23, 95% CI: 1.97-8.52, p < 0.001, respectively)。在高危中风人群中,颈动脉粥样硬化的患病率非常高。特定的 SNPs、它们之间的相互作用以及颈动脉粥样硬化与缺血性脑卒中和其他血管事件的高风险独立相关。
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Inflammation and endothelial function relevant genetic polymorphisms, carotid atherosclerosis, and vascular events in high-risk stroke population
To identify the associations of 19 single nucleotide polymorphisms (SNPs) in genes involved in inflammation and endothelial function and carotid atherosclerosis with subsequent ischemic stroke and other vascular events in the high-risk stroke population.This was a multicenter community-based sectional survey and prospective cohort study in Sichuan, southwestern China. Eight communities were randomly selected, and the residents in each community were surveyed using a structured face-to-face questionnaire. Carotid ultrasonography and DNA information were obtained from 2,377 out of 2,893 individuals belonging to a high-risk stroke population. Genotypes of the 19 SNPs in genes involved in inflammation and endothelial function were measured. All the 2,377 subjects were followed up for 4.7 years after the face-to-face survey. The primary outcome was ischemic stroke, and the secondary outcome was a composite of vascular events.Among the 2,377 subjects, 2,205 (92.8%) completed a 4.7-year follow-up, 947 (42.9%) had carotid atherosclerosis [372 (16.9%) carotid vulnerable plaque, 405 (18.4%) mean IMT > 0.9 mm, 285 (12.0%) carotid stenosis ≥15%]. Outcomes occurred in 158 (7.2%) subjects [92 (4.2%) ischemic stroke, 17 (0.8%) hemorrhagic stroke, 48 (2.2%) myocardial infarction, and 26 (1.2%) death] during follow-up. There was a significant gene–gene interaction among ITGA2 rs1991013, IL1A rs1609682, and HABP2 rs7923349 in the 19 SNPs. The multivariate logistic regression model revealed that carotid atherosclerosis and the high-risk interactive genotypes among the three SNPs were independent with a higher risk for ischemic stroke (OR = 2.67, 95% CI: 1.52–6.78, p = 0.004; and OR = 3.11, 95% CI: 2.12–9.27, p < 0.001, respectively) and composite vascular events (OR = 3.04, 95% CI: 1.46–6.35, p < 0.001; and OR = 3.23, 95% CI: 1.97–8.52, p < 0.001, respectively).The prevalence of carotid atherosclerosis was shown to be very high in the high-risk stroke population. Specific SNPs, interactions among them, and carotid atherosclerosis were independently associated with a higher risk of ischemic stroke and other vascular events.
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