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中国急性冠状动脉综合征患者 CYP2C19 多态性与氯吡格雷抵抗的相关性。

Association of CYP2C19 Polymorphism with Clopidogrel Resistance in Patients with Acute Coronary Syndrome in China.

机构信息

Department of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, China (mainland).

Nanchong Key Laboratory of Individualized Drug Therapy, Nanchong, Sichuan, China (mainland).

出版信息

Med Sci Monit. 2019 Sep 23;25:7138-7148. doi: 10.12659/MSM.915971.

Abstract

BACKGROUND The relationship between clopidogrel-resistance (CR) and polymorphism located in genes encoding clopidogrel metabolism-related enzymes has not been fully explored. Thus far, few studies on CR-associated polymorphism have been conducted in the Chinese population. The purpose of this study was to identify CYP2C19 polymorphism associated with CR in patients with acute coronary syndrome in China. MATERIAL AND METHODS There were 125 patients with acute coronary syndromes (ACS) selected for this study. Of these, 27 patients (21.6%) showed CR (less than 10% reduction in platelet accumulation rate), while the remaining 98 patients (78.4%) were non-clopidogrel-resistant (NCR). RESULTS There were significant differences in the allele frequencies of CYP2C19 (rs4244285) (P=0.03) and CYP2C19 (rs4986893) (P=0.005) between the 2 groups; however, there was no significant difference in allele frequencies of ABCB1 (rs1045642) (P=0.661) and PON1 (rs662) (P=0.690) between the 2 groups. The null allele in the CYP2C19 (rs4244285) [odds ratio (OR)=5.317, 95% confidence interval (CI) 1.542-26.428, P=0.001] and CYP2C19 (rs4986893) (OR=4.295, 95%CI 1.312-17.517, P=0.013) is one of the causes of CR in patients with ACS in China. CONCLUSIONS The CYP2C19 polymorphism (rs4244285 and rs4986893) is the correlative factor of CR in patients with ACS in China. It was found that the null allele in the CYP2C19 polymorphism was related to the higher CR risk. According to the key role of CYP2C19 in the clopidogrel activation and the evaluated role of CYP2C19 in this study, further studies should be carried out to formulate therapeutic alternative methods for CR in patients with ACS.

摘要

背景

氯吡格雷抵抗(CR)与编码氯吡格雷代谢相关酶的基因多态性之间的关系尚未完全阐明。迄今为止,在中国人群中进行的与 CR 相关的多态性研究很少。本研究的目的是确定与中国急性冠状动脉综合征(ACS)患者 CR 相关的 CYP2C19 多态性。

材料与方法

本研究共纳入 125 例 ACS 患者。其中,27 例(21.6%)患者出现 CR(血小板聚集率降低小于 10%),98 例(78.4%)患者为非氯吡格雷抵抗(NCR)。

结果

两组 CYP2C19(rs4244285)(P=0.03)和 CYP2C19(rs4986893)(P=0.005)等位基因频率存在显著差异;而两组 ABCB1(rs1045642)(P=0.661)和 PON1(rs662)(P=0.690)等位基因频率无显著差异。CYP2C19(rs4244285)[比值比(OR)=5.317,95%置信区间(CI)1.542-26.428,P=0.001]和 CYP2C19(rs4986893)(OR=4.295,95%CI 1.312-17.517,P=0.013)的无效等位基因是中国 ACS 患者 CR 的原因之一。

结论

CYP2C19 多态性(rs4244285 和 rs4986893)是中国 ACS 患者 CR 的相关因素。发现 CYP2C19 多态性的无效等位基因与更高的 CR 风险相关。鉴于 CYP2C19 在氯吡格雷激活中的关键作用,以及本研究中 CYP2C19 的评估作用,应进一步开展研究,为 ACS 患者制定针对 CR 的治疗替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7634/6775793/5d00572e31a5/medscimonit-25-7138-g001.jpg

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