谷胱甘肽S-转移酶M1及T1基因突变对抗结核药致肝损伤的影响

The effect of GST M1 and GST T1 gene mutations on anti-tuberculous drug induced hepatic injury

目的探讨谷胱甘肽S-转移酶（GST）M1、T1基因多态性与抗结核药所致肝损伤（ADIH）的相关性。方法2005年8月至2006年7月，采用1：1配对病例对照研究设计，选择从接受抗结核化疗开始随访3个月期间出现肝损伤（病例组106例）及未见肝损伤（对照组106例）的结核病患者，病例组男73例，女33例，年龄15～88岁，平均（49±19）岁；对照组男73例，女33例，年龄17～85岁，平均（49±19）岁。应用PCR技术检测研究对象的GSTM1和GSTT1基因多态性，采用单因素和多因素logistic回归分析GST基因型与ADIH的关系。结果单因素分析结果表明，病例组GSTM1基因缺失型50例（47．2％），明显多于对照组的25例（23．6％），OR值为2．786（95％CI为1．513～5．130）；病例组和对照组GSTT1各基因型频率比较差异无统计学意义；在文化程度、职业、体重指数、吸烟、饮酒和结核类型6个可疑危险因素中，仅体蚕指数和饮酒具有统计学意义。在多因素分析中调整体重指数、饮酒两个因素后，GSTM1基因缺失型仍与ADIH的发生显著相关，OR值为3．022（95％CI为1．540～5．926），仍未发现病例组和对照组GSTT1基因型频率与ADIH的发生有关。结论GSTM1基因缺失型可能是抗结核治疗患者发生肝损伤的易感基因型。

Objective To study the relationship between the polymorphisms of GST M1 and GST T1 genes and anti-tuberculous drug induced hepatic injury （ADIH）. Methods A 1 ： 1 matched case-control study was carried out. One hundred and six patients [ age （49 ± 19 ） years, 73 men and 33 women ] fulfilling the criteria of ADIH during the 3 month follow-up after the initiation of anti-tuberculous therapy were included, while 106 cases [age （49 ±19） years, 73 men and 33 women] without any hepatic injury served as the controls. The genotypes of GST M1 and GST T1 genetic polymorphisms were detected by polymerase chain reaction （PCR） in patients who received anti-tuberculosis therapy. Using SPSS 11.5 for windows software, univariate and multivariate conditional logistic analyses were conducted for studying the relationship between the polymorphisms and ADIH. Results Univariate analysis demonstrated that the ＂null＂ genotype of GST M1 gene occurred in 50 （47.2%） of the cases, more frequent than in the controls [25 （23.6%） ] , with a crude OR （95% CI） 2. 786 （ 1. 513 - 5. 130）. No significant association was observed between ADIH and GST T! polymorphism. Among the risk factors analyzed, body mass index and alcohol drinking were significantly associated with ADIH. In the multivariate analysis, a significant association between ADIH and the ＂null＂ genotype of GST M1 existed, after adjusting for body mass index and drinking status, adjusted OR （ 95% CI） being 3. 022 （ 1. 540 - 5. 926 ） . Again, no significant association was observed between GST T1 polymorphism and ADIH. Conclusion This study demonstrated that patients carrying GST M1-＂ null＂ genotype may be susceptible to ADIH.