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CYP 代谢途径相关基因多态性增加了中国东南部栓塞性和动脉粥样血栓性卒中及易损颈动脉斑块的风险。

CYP metabolic pathway related gene polymorphism increases the risk of embolic and atherothrombotic stroke and vulnerable carotid plaque in southeast China.

机构信息

Department of Neurology, Wenling First People's Hospital of Zhejiang Province, Taizhou 317500, Zhejiang, China.

Department of Neurology, People's Hospital of Deyang City, Deyang 618000, Sichuan, China.

出版信息

J Stroke Cerebrovasc Dis. 2023 Aug;32(8):107195. doi: 10.1016/j.jstrokecerebrovasdis.2023.107195. Epub 2023 May 28.

Abstract

OBJECTIVE

To investigate the association of CYP metabolic pathway-related genetic polymorphisms with the susceptibility to ischemic stroke and stability of carotid plaque in southeast China.

METHODS

We consecutively enrolled 294 acute ischemic stroke patients with carotid plaque and 282 controls from Wenling First People's Hospital. The patients were divided into the carotid vulnerable plaque group and stable plaque group according to the results of carotid B-mode ultrasonography. Polymorphisms of CYP3A5 (G6986A, rs776746), CYP2C92 (C430T, rs1799853), CYP2C93 (A1075C, rs1057910), and EPHX2 (G860A, rs751141) were determined using polymerase chain reaction and mass spectrometry analysis.

RESULTS

EPHX2 GG may reduce the susceptibility to ischemic stroke (OR = 0.520, 95% CI: 0.288 ∼ 0.940, P = 0.030) and AA+AG may increase the risk for ischemic stroke (OR = 1.748, 95% CI: 1.001 ∼ 3.052, P = 0.050). The distribution of CYP3A5 genotypes showed significant differences between the vulnerable plaque and stable plaque groups (P = 0.026). Multivariate logistic regression analysis found that CYP3A5 GG could reduce the risk of vulnerable plaques (OR = 0.405, 95% CI: 0.178 ∼ 0.920, P = 0.031).

CONCLUSION

EPHX2 G860A polymorphism may reduce the stroke susceptibility, while other SNPs of CYP genes are not associated with ischemic stroke in southeast China. Furthermore CYP3A5 polymorphism was related with carotid plaque instability.

摘要

目的

探讨细胞色素 P450 代谢途径相关基因多态性与中国东南部缺血性脑卒中易感性及颈动脉斑块稳定性的关系。

方法

连续纳入温岭市第一人民医院 294 例颈动脉斑块伴急性缺血性脑卒中患者和 282 例对照。根据颈动脉 B 型超声结果将患者分为颈动脉易损斑块组和稳定斑块组。采用聚合酶链反应和质谱分析技术检测 CYP3A5(G6986A,rs776746)、CYP2C92(C430T,rs1799853)、CYP2C93(A1075C,rs1057910)和 EPHX2(G860A,rs751141)的多态性。

结果

EPHX2 GG 可能降低缺血性脑卒中的易感性(OR=0.520,95%CI:0.288~0.940,P=0.030),AA+AG 可能增加缺血性脑卒中的风险(OR=1.748,95%CI:1.001~3.052,P=0.050)。易损斑块组和稳定斑块组 CYP3A5 基因型分布存在显著差异(P=0.026)。多因素 logistic 回归分析发现 CYP3A5 GG 可降低易损斑块的风险(OR=0.405,95%CI:0.178~0.920,P=0.031)。

结论

EPHX2 G860A 多态性可能降低脑卒中的易感性,而中国东南部其他 CYP 基因的 SNPs 与缺血性脑卒中无关。此外,CYP3A5 多态性与颈动脉斑块不稳定有关。

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