急性冠脉综合征患者CYP2C19基因多态性与氯吡格雷疗效的关系

Correlation between CYP2C19 gene polymorphism and clopidogrel efficacy in patients with acute coronary syndrome

目的探讨急性冠状动脉(冠脉)综合征患者CYP2C19基因多态性与氯吡格雷疗效的关系。方法42例急性冠脉综合征患者,根据CYP2C19基因多态性分为A组(正常代谢+快代谢型,23例)和B组(中间代谢+慢代谢型,19例)。两组患者均行CYP2C19基因型检测、血栓弹力图检测。观察比较两组患者二磷酸腺苷(ADP)抑制情况、ADP抑制率,并统计基因分型。结果A组中野生型纯合子组包括正常代谢型患者23例,均为CYP2C19^*1/^*1基因型;快代谢型0例。B组中野生型与突变基因杂合子组包括中间代谢型患者15例,其中CYP2C19^*1/^*2基因型13例,CYP2C19^*1/^*3基因型2例;突变基因纯合子或杂合子组包括慢代谢型患者4例,其中CYP2C19^*2/^*2基因型3例,CYP2C19^*2/^*3基因型1例。B组中ADP抑制率<30%的发生率为58%,高于A组的57%,但差异无统计学意义(P>0.05)。42例患者中服用氯吡格雷后ADP抑制率<30%患者24例(57%),其中停用氯吡格雷更换为替格瑞洛继续服用患者14例(33%),14例患者中替格瑞洛顿服12 h后复查血小板ADP抑制率均>30%患者13例(31%),但仍有ADP抑制率<30%患者1例(2%)。A组平均ADP抑制率为(39.5±28.4)%,B组平均ADP抑制率为(31.5±21.6)%,B组平均ADP抑制率低于A组,但差异无统计学意义(P>0.05)。结论本研究结果支持CYP2C19多态性仅为众多影响氯吡格雷疗效的因素之一,并不能最终决定氯吡格雷疗效。氯吡格雷服用后的抗血小板聚集疗效,还受众多其他因素的影响,仍需进一步研究。

Objective To discuss the correlation between CYP2C19 gene polymorphism and clopidogrel efficacy in patients with acute coronary syndrome.Methods A total of 42 patients with acute coronary syndrome were divided into two groups:group A(normal metabolism type+fast metabolism type,23 cases)and group B(intermediate metabolism type+slow metabolism type,19 cases)according to CYP2C19 gene polymorphism.All patients were tested for CYP2C19 genotype and thromboelastography.The general information,adenosine diphosphate(ADP)inhibition,CYP2C19 gene polymorphism and ADP inhibition rate of the two groups were observed and compared,and the genotypes were analyzed.Results In group A,the wildtype homozygous group included 23 patients with normal metabolic type,all of whom were CYP2C19^*1/^*1 genotype,and 0 patient with fast metabolic type.In group B,the heterozygotes of wild type and mutant gene group included 15 patients with intermediate metabolism,of which 13 patients with CYP2C19^*1/^*2 genotype and 2 patients with CYP2C19^*1/^*3 genotype.The homozygous or heterozygous group of the mutant gene included 4 patients with slow metabolism,of which 3 patients with CYP2C19*2/*2 genotype and 1 patient with CYP2C19^*2/^*3 genotype.The incidence of ADP inhibition rate<30%was 58%in group B,which was higher than 57%in group A,but the difference was not statistically significant(P>0.05).Of the 42 patients,24 cases(57%)had ADP inhibition rate<30%after taking clopidogrel,of which 14 cases(33%)who discontinued clopidogrel and changed to telgrelor.Among the 14 patients,13 cases(31%)had platelet ADP inhibition rate>30%after 12 h of tegriloton administration,but 1 case(2%)had ADP inhibition rate of<30%.The mean ADP inhibition rate was(39.5±28.4)%in group A,which was(31.5±21.6)%in group B,the mean ADP inhibition rate in group B was lower than that in group A,but the difference was not statistically significant(P>0.05).Conclusion The results of this study support that CYP2C19 polymorphism is only one of the factors that affect the efficacy of clopidogrel,and cannot ultimately determine the efficacy of clopidogrel.The anti-platelet aggregation effect of clopidogrel is also influenced by many other factors,which need further study.