CYP2C19基因多态性与抗结核药物性肝损害的关系研究Δ

目的:探讨肝药酶细胞色素P4502C19(CYP2C19)基因多态性与抗结核药物性肝损害(ATDIH)易感性的关系。方法:采用回顾性病例对照研究方法,采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法对ATDIH病例组106例与抗结核治疗无肝损害的对照组103例的CYP2C19*2和CYP2C19*3位点进行基因型分型,分析基因多态性与ATDIH的相关性。结果:病例组与对照组CYP2C19*2和CYP2C19*3基因表型频率差异无统计学意义(P>0.05)。根据CYP2C19*2和CYP2C19*3双基因表型的代谢速度分为快代谢型、中间代谢型和慢代谢型。Logistic回归分析表明,慢代谢型患者出现肝损害的危险性是快代谢型的2.657倍(95%CI=1.089⁶.482)。结论:汉族人群CYP2C19*2和CYP2C19*3基因多态性可能与ATDIH的发生有关,慢代谢型患者较快代谢型患者更易出现肝损害。

Relationship between Genetic Polymorphism of CYP2C19 and Anti-tuberculosis Drug-induced Hepatotoxicity

OBJECTIVE： To investigate the relationship between the genetic polymorphisms of CYP2C19 and susceptibility of anti-tuberculosis drug-induced hepatotoxicity （ATDIH） in the tuberculosis patients. METHODS： With retrospective case-control study, genetic polymorphisms of CYP2C19 were analyzed using PCR-RFLP in 106 cases of ATDIH group and 103 case without AT- DIH of control group. The relationship of genetic polymorphisms with ATDIH was analyzed. RESULTS： There was no statistical sig- nificance in frequency of CYP2C19＂2 or CYP2C19＂3 genotype between ATDIH group and control group （P〉0.05）. The genotypes that CYP2C19＂2 combined with CYP2C19＂3 were divided into three types according to metabolism rate of their double gene pheno- type： rapid type, intermediate type and slow type. Logistic regression analysis demonstrated that ATDIH risk with slow metabolizer was 2.657 times of rapid metabolizer （95%CI=1.089-6.482）. CONCLUSIONS： CYP2C19＂2 and CYP2C19＂3 genotypes might have association with the risk of ATDIH. The incidence of ATDIH in slow metabolizer is higher than that in rapid metabolizer.