重庆地区心脑血管疾病氯吡格雷抵抗与CYP2C19基因多态性等影响因素研究

Correlation Between Clopidogrel Resistance and CYP2C19 Gene Polymorphisms in Patients with Cardiovascular Disease in Chongqing

目的探讨重庆地区汉族人群CYP2C19基因多态性与脑血管疾病患者服药后产生氯吡格雷抵抗(CR)的相关性。方法纳入医院神内科2017年6月至2018年5月需用氯吡格雷治疗的心脑血管疾病患者526例,分别于服用氯吡格雷前行CYP2C19基因型、二磷酸腺苷(ADP)诱导的血小板聚集率、血糖、C反应蛋白、凝血时间等指标检测,服药后24 h复测ADP诱导的最大血小板聚集率(MAP),用荧光染色原位杂交测序检测系统确定基因型,根据不同基因型对患者进行分组。结果 526例患者中,CYP2C19基因CYP2C19*1/*17为超快代谢型,共5例(0. 95%);CYP2C19*1/*1为快代谢型,共213例(40. 49%);CYP2C19*2/*17,CYP2C19*3/*17,CYP2C19*1/*2,CYP2C19*1/*3为中代谢型,共230例(43. 73%);CYP2C19*2/*2,CYP2C19*2/*3为慢代谢型,共78例(14. 83%)。发生CR 73例(13. 88%),其中超快代谢组、快代谢组、中代谢组、慢代谢组患者发生CR的例数分别为0例、26例(12. 21%)、33例(14. 35%)、14例(17. 95%),差异有统计学意义(P <0. 05);慢代谢组血小板聚集率均较超快代谢组、快代谢组、中代谢组高。结论心脑血管患者CYP2C19基因多态性与氯吡格雷抵抗存在相关性,慢代谢基因型较其他基因型患者常规使用CR风险高。

Objective To investigate the correlation between CYP2 C19 gene polymorphisms and clopidogrel resistance( CR) in patients with cardiovascular disease( CVD) in Chongqing Han population. Methods Totally 526 patients with CVD who need to be treated with clopidogrel in the Department of Neurology of our hospital from June 2017 to May 2018 were selected. The CYP2 C19 genotype,adenosine diphosphate( ADP)-induced platelet aggregation rate,blood glucose,C-reactive protein,clotting time and other indicators were detected before taking clopidogrel. The ADP-induced maximum platelet aggregation rate was retested at 24 h after administration,and genotypes were determined by the detection system of fluorescence in situ hybridization,and the patients were grouped according to different genotypes. Results In 526 patients,5( 0. 95%) patients were the ultrafast metabolism type with CYP2 C19 * 1/* 17 gene,213( 40. 49%) patients were the fast metabolism type with CYP2 C19*1/*1 gene,230( 43. 73%) patients were the moderate metabolism type with CYP2 C19 *2/*17 gene,CYP2 C19*3/*17 gene,CYP2 C19*1/*2 gene and CYP2 C19*1/*3 gene,and 78( 14. 83%)patients were the slow metabolism type with CYP2 C19 * 2/* 2 gene and CYP2 C19 * 2/* 3 gene. Totally 73( 13. 88%) patients had CR,among which the patients in the ultrafast metabolism group,fast metabolism group and moderate metabolism group and slow metabolism group was 0 case,26 cases( 12. 21%),33 cases( 14. 35%) and 14 cases( 17. 95%),respectively,the distribution difference was statistically significant( P < 0. 05). The platelet aggregation rate of slow metabolism group was higher than that of ultrafast metabolism group,fast metabolism group and moderate metabolism group. Conclusion CYP2 C19 gene polymorphism is correlated to clopidogrel resistance in the patients with CVD,and the risk of CR in patients with slow metabolism genotype is higher than that in patients with other genotypes.