CYP2C19基因多态性与呼和浩特地区急性脑梗死氯吡格雷抵抗的相关性分析

目的　探讨急性脑梗死氯吡格雷抵抗与CYP2C19基因多态性的相关性。方法　纳入2018年5月1日至2019年10月30日在内蒙古自治区人民医院神经内科住院的急性脑梗死患者181例，男105例，女76例，年龄43～85岁。根据CYP2C19基因分型分为快代谢型（CYP2C19*1/*1）、中代谢型（CYP2C19* 1/*2、CYP2C19*1/*3）和慢代谢型（CYP2C19*2/*2、CYP2C19 *2/*3、CYP2C19*3/*3）。比较患者的年龄、吸烟史、饮酒史、糖尿病、高血压、高脂血症、同型半胱氨酸、美国国立卫生研究院卒中量表（NIHSS）评分和基因型。组间比较采用χ²检验和方差分析，P<0.05为差异有统计学意义。结果　181例急性脑梗死患者中，快代谢型92例（50.83%）、中代谢型69例（38.12%）、慢代谢型20例（11.05%）。年龄、性别、糖尿病、高血压、高脂血症、同型半胱氨酸与氯吡格雷抵抗无相关性（均P>0.05）；快代谢型组NIHSS评分为（3.29±2.14）分，中代谢型组为（3.83±2.47）分，慢代谢型组为（5.90±3.81）分，NIHSS评分与氯吡格雷抵抗相关（P<0.01）。3组急性脑梗死患者随访1年，终点事件发生率快代谢型为3.26%（3/92）、中代谢型为5.80%（4/69）、慢代谢型为20.00%（4/20）。根据CYP2C19基因型，生存分析Log-Rank检验，快代谢型和慢代谢型比较差异有统计学意义（χ²=7.856，P=0.005）。结论　急性脑梗死患者CYP2C19基因代谢型可影响氯吡格雷的抗血小板作用和临床疗效，携带CYP2C19*3/*3的急性脑梗死患者氯吡格雷反应性低。呼和浩特地区急性脑梗死患者主要为快代谢型和中代谢型，其中慢代谢型急性脑梗死复发率较中、快代谢型高。

Correlation between gene polymorphism of CYP2C19 and clopidogrel resistance in patients with acute cerebral infarction in Hohhot area

Objective:To observe the correlation between the gene polymorphism of CYP2C19 and clopidogrel resistance in patients with acute cerebral infarction.Methods:From May 1, 2018 to October 30, 2019, 181 patients with acute cerebral infarction treated at Department of Neurology, Inner Mongolia People's Hospital were included, including 105 males and 76 females, and they were 43~85 years old. The CYP2C19 genotypes were divided into an extensive metabolism type (CYP2C19*1/*1), an intermediate metabolism type (CYP2C19* 1/*2 and CYP2C19*1/*3), and a slow metabolism type (CYP2C19*2/*2, CYP2C19*2/*3, and CYP2C19*3/*3). The patients' age, smoking, alcohol consumption, diabetes, hypertension, hyperlipidemia, homocysteine, National Institute of Health Stroke Scale (NIHSS) score, and genotypes were compared. χ2 test and rariance analysis were used for the comparison between the groups. If P<0.05, there is a statistical difference. Results:Among the 181 patients, 92 cases (50.83%) were of the extensive metabolism type, 69 (38.12%) the intermediate metabolism type, and 20 (11.05%) the slow metabolism type. The age, gender, diabetes, hypertension, hyperlipidemia, and homocysteine had no correlation with clopidogrel resistance (all P>0.05). The NIHSS score was (3.29±2.14) in the extensive metabolism type group, (3.83±2.47) in the intermediate metabolism type group, and (5.90±3.81) in the slow metabolism type group, so the NIHSS score was correlated with clopidogrel resistance ( P<0.01). The 3 groups were followed up for 1 year, and the incidence of endpoint events was 3.26% (3/92) in the extensive metabolism type group, 5.80% (4/69) in the intermediate metabolism type group, and 20.00% (4/20) in the slow metabolism type group. According to the CYP2C19 genotypes, the Log-Rank test for the survival analysis showed that there was a statistical difference between the extensive metabolism type group and the slow-metabolism group ( χ2=7.856, P=0.005). Conclusions:The CYP2C19 genotype can affect the clinical efficacy and antiplatelet effect of clopidogrel for patients with acute cerebral infarction. Clopidogrel has a low response in patients with acute cerebral infarction who carry CYP2C19*3/*3. Patients with acute cerebral infarction in Hohhot area are mainly of the extensive metabolism type and intermediate metabolism type. The recurrence rate of the slow metabolism type is higher than those of the extensive metabolism type and intermediate metabolism type.