抗结核药物性肝损害与CYP2E1和GSTM1基因多态性的相关性研究

Association of Antituberculosis Drug-induced Hepatotoxicity with CYP2E1 and GSTM1 Gene Polymorphisms

目的:分析抗结核药物性肝损害(ADIH)与细胞色素P450酶(CYP)2E1和谷胱甘肽-S-转移酶(GST)M1基因多态性的相关性,并探讨其易感因素。方法:选择我院2011年10月-2015年6月收治的我国南方汉族肺结核住院患者91例,根据治疗过程中是否出现ADIH将其分为ADIH组(34例)和无ADIH组(57例);抽取患者外周静脉血,分别采用聚合酶链式反应(PCR)和多重PCR法检测其CYP2E1和GSTM1基因多态性,采用Logistic回归分析考察ADIH的易感因素。结果:所有患者CYP2E1基因型均为c2/c2型(100%);GSTM1基因型分布符合Hardy-Weinberg平衡(P>0.05)。ADIH组GSTM1(+/-)基因型患者有9例(26.5%),GSTM1(-/-)基因型患者有25例(73.5%),差异有统计学意义(P<0.05);无ADIH组GSTM1(+/-)基因型患者有17例(29.8%),GSTM1(-/-)基因型患者有40例(70.2%),差异有统计学意义(P<0.05);但GSTM1(+/-)和(-/-)基因型在两组患者中的分布差异均无统计学意义(P>0.05)。Logistic回归分析结果显示,患者性别、年龄、体质量指数和GSTM1基因型与ADIH均无相关性(P>0.05)。结论:患者性别、年龄、体质量指数和GSTM1基因型可能与ADIH无关。由于仅检出1种CYP2E1基因型,尚无法判断其多态性与ADIH的相关性。

OBJECTIVE： To analyze the association of antituberculosis drug-induced hepatotoxicity （ADIH） with gene polymorphisms of cyptochrome P,50 （CYP） 2El and glutathione-S-transferase （GST） M1, and to discuss susceptibility factor. METHODS ： 91 southern and Han inpatients with tuberculosis were selected from our hospital during Oct. 2011-Jun. 2015. According to the occurrence of ADIH, those patients were divided into ADIH group （34 cases） and non-ADIH group （57 cases）. Peripheral venous blood of pa- tients were collected, PCR and multiple PCR were used to detect CYP2E1 and GSTM1 gene polymorphisms. The susceptibility factors of ADIH was investigated by Logistic regression analysis. RESULTS： CYP2Et genotype of all patients were c2/c2 genotype （100 % ）, and GSTM1 genotype distribution met Hardy-Weinberg balance （P〉0.05）. There were 9 patients （26.5%） with GSTM1 （＋/-）genotype and 25 patients （73.5%） with GSTM1 （-/-） genotype in ADIH group, with statistical significance （P〈0.05）. There were 17 patients （29.8%） with GSTM1 （＋/-）genotype and 40 patients （70.2%） with GSTM1 （-/-） genotype in non-ADIH group, with statistical significance （ P〈 0.05）. There was no statistical significance in the distribution of GSTM1 （＋/-） and （ - / - ） genotype between 2 groups （P〉0.05）. Logistic regression analysis showed that there was no correlation of gender, age, BMI and GSTM1 genotype with ADIH （P〉0.05）. CONCLUSIONS： Gender, age, BMI and GSTM1 genotype may be not correlated with AD1H; The relationship of GSTM1 genotype with ADIH can not be judged because only one kind of CYP2E1 genotype has been detected.