CYP2C19和ABCB1 C3435T基因多态性与氯吡格雷给药后ADP抑制率的关系

Association of CYP2C19 and ABCB1 C3435T gene polymorphisms with ADP inhibition after clopidogrel administration

目的 分析CYP2C19和ABCB1 C3435T基因多态性与氯吡格雷个体化给药后二磷酸腺酐(ADP)抑制率的关系。方法 选取2017年12月—2021年1月中山大学附属第五医院神经内科和脑血管病科确诊的脑梗死或短暂性脑缺血并服用氯吡格雷抗血小板治疗的住院患者138例,所有患者均给予氯吡格雷75 mg治疗7 d后,检测患者ADP抑制率,同时利用荧光原位杂交法,检测患者CYP2C19和ABCB1 C3435T基因多态性,分析基因多态性与ADP抑制率的关系。结果 男性患者与女性患者对氯吡格雷的反应性存在显著差异(χ^(2)=6.807,P=0.033),男性患者ADP抑制率高于女性患者(t=2.686,P=0.008)。CYP2C19超快代谢型、快代谢型、中间代谢型和慢代谢型的ADP抑制率差异无统计学意义(F=1.129,P=0.340)。CYP2C19*1/*17型、*1/*1型、*1/*2型、*1/*3型、*2/*2型和*2/*3型的ADP抑制率有逐步下降的趋势,但差异无统计学意义(F=1.756,P=0.126),组间两两比较显示,*1/*1型的ADP抑制率高于*2/*2型(t=2.257,P=0.036)。ABCB1 C3435T的CC型、CT型和TT型的ADP抑制率比较差异无统计学意义(F=0.555,P=0.576)。CYP2C19快代谢型、中间代谢型和慢代谢型中ABCB1 C3435T不同基因型(CC型、CT型和TT型)的ADP抑制率比较差异均无统计学意义(F/P=0.192/0.826、0.525/0.594、0.666/0.540)。男性患者与女性患者在CYP2C19各代谢型中的分布无显著差异(U=2 146.50,P=0.608)。结论 在氯吡格雷个体化治疗中,CYP2C19基因多态性与ADP抑制率存在一定的相关性,ABCB1 C3435T基因多态性与ADP抑制率无相关性。

Objective To analyze the relationship between CYP2C19 and ABCB1 C3435T gene polymorphisms and the inhibition rate of ADP after individualized administration of clopidogrel.Methods A total of 138 hospitalized patients with cerebral infarction or transient cerebral ischemia and taking clopidogrel antiplatelet therapy who were diagnosed in the Department of neurology and Department of cerebrovascular,the Fifth Affiliated Hospital of Sun Yat-sen University and diagnosed with cerebral infarction or transient cerebral ischemia and taking clopidogrel antiplatelet therapy from December 2017 to January 2021 were selected,and all of the patients were given 75 mg of clopidogrel for 7 days.The rate of ADP inhibition was detected,the patients were utilized to detect the fluorescence At the same time,fluorescence in situ hybridization was used to detect the polymorphisms of CYP2C19 and ABCB1 C3435T genes in the patients,and to analyze the relationship between the gene polymorphisms and ADP inhibition rate.Results The difference in responsiveness to clopidogrel between male and female patients was statistically significant(χ^(2)=6.807,P=0.033),and the rate of ADP inhibition in male patients was higher than in female patients(t =2.686,P=0.008).The difference in ADP inhibition rates of CYP2C19 ultrafast metabolizers,fast metabolizers,intermediate metabolizers and slow metabolizers were not statistically significant(F=1.129,P=0.340).There was a gradual decrease in the ADP inhibition rate of CYP2C19 *1/*17,*1/*1,*1/*2,*1/*3,*2/*2,and *2/*3 types,but the difference was not statistically significant(F=1.756,P =0.126),and the results of two-by-two comparison between groups showed that the ADP inhibition rate of *1/*1 type was higher than that of *2/*2 type(t=2.257,P=0.036).There was no statistically significant difference in ADP inhibition rate comparing CC,CT and TT types of ABCB1 C3435T(F=0.555,P=0.576).The differences in the comparison of ADP inhibition rates of different genotypes(CC,CT,and TT) of ABCB1 C3435T in CYP2C19 fast metabolizers,intermediate metabolizers,and slow metabolizers were not statistically significant(F/P=0.192/0.826,0.525/0.594,0.666/0.540).There was no significant difference in the distribution of CYP2C19 metabolotypes between male and female patients(U=2,146.50,P=0.608).Conclusion In the individualized treatment of clopidogrel,there is a correlation between CYP2C19 gene polymorphism and ADP inhibition rate,and no correlation between ABCB1 C3435T gene polymorphism and ADP inhibition rate.