细胞色素P450酶2C19基因多态性对TIPS术后患者服用氯吡格雷效果的影响

The influence of CYP2C19 gene polymorphism on the curative effect of clopidogrel in patients after receiving TIPS

目的评估细胞色素P450酶2C19(CYP2C19)基因多态性对经颈静脉肝内门体分流术(TIPS)肝硬化患者术后服用氯吡格雷抗血小板治疗的影响。方法收集2013年1月至2014年12月接受TIPS术治疗的171例肝硬化患者临床资料。所有患者均于术中采集门静脉及肘静脉血液样本并行CYP2C19基因检测。术后每3个月临床随访,比较分析基因检测结果与临床随访结果。结果 110例TIPS术前无输血且术后规律服用氯吡格雷患者纳入本研究。术后平均服用氯吡格雷时间为192.4 d(31~517 d),门静脉血及肘静脉血基因检测结果一致,CYP2C19基因型为*1/*1有49例(44.5%)、*1/*2有27例(24.6%)、*1/*3有18例(16.4%)、*2/*2有11例(10.0%)、*2/*3有3例(2.7%)、*3/*3有2例(1.8%);随访显示慢代谢型基因携带患者分流道功能异常发生率为87.5%(14/16),较中等代谢型患者(20.0%,9/45,χ2=22.9,P=0.006)及快代谢型患者(8.2%,4/49,χ2=37.91,P=0.000 1)明显增高;Cox回归模型多变量分析提示CYP2C19慢代谢型基因变异,是分流道功能异常的重要预测因素(95%CI 1.80~9.03,P=0.000 7)。结论 CYP2C19慢代谢基因变异(*2/*2、*2/*3、*3/*3)是影响TIPS术后患者氯吡格雷治疗效果的重要因素之一,术前检测可为术后提供较为有效的抗血小板治疗方案。

Objective To evaluate the effect of cytochrome P450 isoenzyme subfamily 2C 19 （CYP2C19） gene polymorphism on the clopidogrel antiplatelet therapy in cirrhosis patients after receiving transjugular intrahepatic portosystemic shunt （TIPS）. Methods The clinical data of 171 cirrhosis patients, who were treated with TIPS during the period from January 2013 to December 2014, were retrospectively analyzed. During operation both the portal vein and the elbow vein blood samples were collected and sent for CYP2C19 gene testing. After TIPS, clinical follow-up checkup was made once every 3 months. The gene detection results and clinical follow-up findings were comparatively analyzed. Results A total of 110 patients, who had not received blood transfusion before TIPS and who had regularly taken clopidogrel antiplatelet therapy after TIPS were enrolled in the study. The mean time to take clopidogrel was 192.4 days （31-517 days）, and the gene detection results of portal vein and elbow vein were quite consistent. CYP2C19 genotype of ＊1/＊1 was found in 49 patients （44.5%）, CYP2C19 genotype of ＊1/＊2 in 27 patients （24.6%）, CYP2C19 genotype of ＊1/＊3 in 18 patients （16.4%）, CYP2C19 genotype of ＊2/＊2 in 11 patients （10.0%）, CYP2C19 genotype of ＊2/＊3 in 3 patients （2.7%）, and CYP2C 19 genotype of ＊3/＊3 in 2 patients （1.8%）. Following-up examinations showed that the incidence of shunt dysfunction in patients carrying slow metabolic gene was 87.5% （14/16）, which was significantly higher than that in patients carrying moderate metabolic gene （20.0%, 9/45 ; χ^2=22.9, P=0.006） as well as in patients carrying fast metabolic gene （8.2%, 4/49;χ^2=37.91, P=0.000 1）. Multivariate analysis of Cox regression model indicated that CYP2C19 slow metabolic gene variation was an important predictive factor for shunt dysfunction （95%CI：1.80-9.03, P=-0.000 7）. Conclusion CYP2C19 slow metabolic gene variation, including genotype of ＊2/＊2,＊2/＊3 and ＊3/＊3, is an important factor that can influence the efficacy of clopidogrel treatment after TIPS. Preoperative CYP2C19 gene detection results can provide useful information, which is very helpful in making an effective and reliable anti-platelet treatment plan for patients after TIPS.