GSTM1、GSTT1基因多态性与抗结核药物致肝损害的相关性研究

摘要

目的 探讨GSTM1、GSTT1 基因多态性与抗结核药物致肝损害(ATDH)易感性之间的关系.方法该研究采用前瞻性设计,纳入2012年10月至2014年12月四川大学华西医院的结核病患者,并规律抗结核治疗至少3个月,分别于服药2、4周和2、3月时随访肝功能,以此评估患者肝功能情况.当发生肝功能损害时,即被纳入病例组,相反,则被纳入对照组.采用聚合酶链反应及琼脂糖凝胶电泳方法,检测GSTM1、GSTT1基因是否缺失并分析基因多态性.结果 该研究共纳入247例新发结核病患者,随访3个月后,病例组24例,对照组223例.两组中GSTM1 基因缺失的频率分别为 58.33%和 52.47%,差异无统计学意义(P= 0.668);两组中 GSTT1 基因缺失的频率分别为 45.83%和 51.12%,差异无统计学意义(P= 0.674).结论 在中国结核人群中,GSTM1、GSTT1 基因多态性与 ATDH 易感性可能无关,即该基因的缺失可能不会增加 ATDH 的风险.%Objective To investigate the correlation between gene polymorphisms of GSTM1 and GSTT1 and anti-tuberculosis drug-induced hepatotoxicity (ATDH).Methods The prospective study was adopted.The patients with tuberculosis(TB)treated from October of 2012 to December of 2014 in West China Hospital of Sichuan University were selected.All the patients were treated regularly for no less than 3 months and followed up at the 2nd and 4th week and 2nd and 3rd month respectively after taking anti-tuberculosis drugs to evaluate their liver function.The patients with impaired liver function were considered as the case group,while the patients without liver damage were considered as the control group.The methods of polymerase chain reaction(PCR)and agarose gel electrophoresis were used to detect whether there was gene deletion or not in order to analyze the gene polymorphisms of GSTM1 and GSTT1.Results A total of 247 newly-diagnosed TB patients were recruited in this study.Twenty-four cases were recruited in the case group and 223 cases in the control group during the 3-month follow-up.The incidences of GSTM1 gene deletion were 5 8.3 3 % in the case group and 52.47% in the control group,and the difference between the two groups was not statistically significant(P=0.668). The incidences of GSTT1 gene deletion were 45.83% in the case group and 51.12% in the control group,and the difference between the two groups was not statistically significant(P=0.674).Conclusion In the Chinese TB population, The gene polymorphisms of GSTM1 and GSTT1 may not correlated with ATDH susceptibility,i.e.,the gene deletion of GSTM1 and GSTT1 may not increase the risk of ATDH.