Genetic Polymorphisms Of GSTM1 And GSTT1 And Susceptibility To Anti-tuberculosis Drugs Induced Liver Injury

Objective: To investigate the occurrence of anti-tuberculosis drug-induced liver injury(ATLI) and the susceptible factors. To study genetically the relations between ATLI and genetic polymorphisms of GSTM1, GSTT1. Method: From May 2010 to August2012, tuberculosis patients who were registered in the Center for Disease Control of the research sites and accepted standard short course chemotherapy were enrolled in our cross-sectional study. With the questionnaire survey, case history materials and liver function tests, the incidence of ATLI and its distribution were investigated. The genotypes of GSTM1 and GSTT1 were determined by through multiplex PCR assay. Unconditional Logistic regression model was used to investigate the impact of genetic polymorphisms of GSTM1, GSTT1 and environmental factors on ATLI. Result: 1.Among the 2791 patients in the research, 108 patients were diagnosed with ATLI and the incidence was 3.9%. 2.The frequency of GSTM1 and GSTT1 ‘null’ genotypes was 45.8% and 24.7%, respectively.3.Univariate analysis results showed that GSTM1 genotype and hepatitis C were influential factors of ATLI(P<0.05). Multivariate analysis results showed that GSTM1 genotype, hepatitis C and historys of alcohol intake were linked to ATLI; compared with the patients with GSTM1 non-null genotype, the risk of ATLI increased among the patients with GSTM1 ‘null’ genotype, OR(95%CI) was 1.552(1.041~2.315); compared with the patients without hepatitis C infection, the risk of ATLI increased among the patients with hepatitis C infection, OR(95%CI) was 3.066(1.132~8.306); compared with the patients without alcohol consumption, the risk of ATLI increased among the patients with historys of alcohol intake, OR(95%CI) was 1.972(1.033~3.765). Among ATLI patients, it was significantly different in the level of ALT between different GSTM1genotypes(P<0.05). 4.With GSTM1 and GSTT1 both non-null genotype as a reference,only GSTM1 null genotype and GSTM1, GSTT1 both null genotype were influential factors of ATLI after adjusting for hepatitis C and history of alcohol intake, their OR(95%CI) were 1.822(1.114 ~ 2.902), 1.761(1.003 ~ 3.093), respectively. Conclusion:GSTM1 null genotype, hepatitis C and historys of alcohol intake may be susceptible factors of ATLI, genetic polymorphism of GSTM1 may be associated with the severity of ATLI.