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高危卒中人群中与炎症和内皮功能相关的基因多态性、颈动脉粥样硬化及血管事件

Inflammation and endothelial function relevant genetic polymorphisms, carotid atherosclerosis, and vascular events in high-risk stroke population.

作者信息

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

机构信息

Department of Neurology, The People's Hospital of Deyang City, Deyang, Sichuan, China.

Department of Neurology, The Second People's Hospital of Deyang City, Deyang, China.

出版信息

Front Neurol. 2024 May 16;15:1405183. doi: 10.3389/fneur.2024.1405183. eCollection 2024.

DOI:10.3389/fneur.2024.1405183
PMID:38827573
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11144032/
Abstract

AIM

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.

METHODS

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.

RESULTS

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 rs1991013, rs1609682, and 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,  = 0.004; and OR = 3.11, 95% CI: 2.12-9.27,  < 0.001, respectively) and composite vascular events (OR = 3.04, 95% CI: 1.46-6.35,  < 0.001; and OR = 3.23, 95% CI: 1.97-8.52,  < 0.001, respectively).

CONCLUSION

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.

摘要

目的

确定参与炎症和内皮功能以及颈动脉粥样硬化的基因中的19个单核苷酸多态性(SNP)与高危卒中人群随后发生的缺血性卒中和其他血管事件之间的关联。

方法

这是一项在中国西南部四川省开展的基于社区的多中心横断面调查和前瞻性队列研究。随机选取8个社区,使用结构化面对面问卷对每个社区的居民进行调查。从2893名高危卒中人群个体中获取了2377人的颈动脉超声检查和DNA信息。检测了参与炎症和内皮功能的基因中19个SNP的基因型。在面对面调查后,对所有2377名受试者进行了4.7年的随访。主要结局为缺血性卒中,次要结局为血管事件的复合终点。

结果

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%)有颈动脉易损斑块,405人(18.4%)平均内膜中层厚度>0.9mm,285人(12.0%)颈动脉狭窄≥15%]。随访期间,158名(7.2%)受试者出现结局[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,26名(1.2%)死亡]。在19个SNP中,rs1991013、rs1609682和rs7923349之间存在显著的基因-基因相互作用。多变量逻辑回归模型显示,颈动脉粥样硬化以及这三个SNP中的高危交互基因型与缺血性卒中和复合血管事件的风险较高独立相关(缺血性卒中的OR分别为2.67,95%CI:1.52-6.78,P=0.004;以及OR为3.11,95%CI:2.12-9.27,P<0.001;复合血管事件的OR分别为3.04,95%CI:1.46-6.35,P<0.001;以及OR为3.23,95%CI:1.97-8.52,P<0.001)。

结论

高危卒中人群中颈动脉粥样硬化的患病率很高。特定的SNP、它们之间的相互作用以及颈动脉粥样硬化与缺血性卒中和其他血管事件的较高风险独立相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d460/11144032/a13bf254f3df/fneur-15-1405183-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d460/11144032/a13bf254f3df/fneur-15-1405183-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d460/11144032/a13bf254f3df/fneur-15-1405183-g001.jpg

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