CYP2C19基因型与氯吡格雷抵抗的相关性研究

Correlation between CYP2C19 genotype and clopidogrel resistance

目的分析CYP2C19基因型与氯吡格雷抵抗的相关性。方法以2015年1月-2018年1月单用氯吡格雷(75 mg,每天1次)进行抗血小板治疗且规律服用1个月以上的患者327例为研究对象,进行CYP2C19基因型检测及血栓弹力图检测,以二磷酸腺苷(ADP抑制率<30%定义为氯吡格雷抵抗。结果 CYP2C19基因超快代谢型(*1/*17、*17/*17) 6例(1. 8%),快代谢型(*1/*1) 127例(38. 8%),中间代谢型(*1/*2、*1/*3、*2/*17、*3/*17) 153例(46. 8%),慢代谢型(*2/*2、*2/*3、*3/*3) 41例(12. 5%)。其中,超快代谢型患者未见氯吡格雷抵抗,快代谢型、中间代谢型及慢代谢型患者的氯吡格雷抵抗例数及占各基因型的比例分别为27例(21. 3%)、55例(35. 9%)、28例(68. 3%),3组间氯吡格雷抵抗率对比具有统计学差异。结论 CYP2C19基因型与氯吡格雷抵抗相关,进行基因型检测可指导临床用药。慢代谢人群具有较高的氯吡格雷抵抗率,此类人群应谨慎选用氯吡格雷,需调整药物使用剂量或加用其他药物联合抗血小板聚集治疗。

Objective To analyze the correlation between CYP2 C19 genotype and clopidogrel resistance. Methods From January 2015 to January 2018,327 patients who received clopidogrel（ 75 mg daily） alone for antiplatelet therapy and took clopidogrel regularly for more than one month were selected as subjects. CYP2 C19 genotyping and thromboela-stogram were performed in selected patients. Clopidogrel resistance was defined as adenosine diphosphate（ ADP） inhibition rate less than 30%. Results CYP2 C19 gene ultrafast metabolism type（＊1/＊17,＊17/＊17） 6 cases（ 1. 8%）,fast metabolism type（＊1/＊1） 127 cases（ 38. 8%）,intermediate metabolism type（＊1/＊2,＊1/＊3,＊2/＊17,＊3/＊17） 153 cases（ 46. 8%）and slow metabolism type（＊2/＊2,＊2/＊3,＊3/＊3） 41 cases（ 12. 5%）. Clopidogrel resistance was not found in patients with ultrafast metabolism. The number of clopidogrel resistant cases and the proportion of clopidogrel resistant cases in fast metabolic type,intermediate metabolic type and slow metabolic type were 27（ 21. 3%）,55（ 35. 9%） and 28（ 68. 3%） respectively. There were significant differences in clopidogrel resistant rates among the three groups. Conclusion CYP2 C19 genotype is associated with clopidogrel resistance. Genotype detection can guide clinical use. Clopidogrel resistance is high in the slow metabolic group. Clopidogrel should be used cautiously in this group. The dosage of clopidogrel should be adjusted or combined with other drugs to treat platelet aggregation.