Genetic polymorphism of glutathione S-transferase T1, M1 and asthma, a meta-analysis of the literature.

Published studies have confirming or refusing an association between either glutathione S-transferase T1 (GSTT1) or M1 (GSTM1) polymorphism and asthma risk. Therefore the present meta-analysis was done. Literature-based meta-analysis was supplemented by tabular data from investigators of all relevant studies of two GST polymorphism (GSTM1 and GSTT1) available before May 2006, with investigation of potential sources of heterogeneity. Included in the resent study were 14 studies, involving a total 2292 asthma patients and 5718 controls. We found substantial evidence of heterogeneity between the studies. Exclusion of two studies with lowest quality scores resulted in a dramatic decrease in heterogeneity. The overall OR of the asthma risk associated with GSTM1 null genotype was 1.20 (95% CI: 1.08-1.35). Stratifying the meta-analysis by age and smoking status of subjects, the pooled ORs for GSTM1 null genotype were 1.56 (95% CI: 1.25-1.94) in adults and 1.95 (95% CI: 1.21-3.13) in non-smokers. The GSTT1 null genotype was associated with asthma risk in non-smoker adults (OR = 2.06, 95% CI: 1.21-3.71). To investigate whether profile of GST genotypes are associated with the risk of the asthma, further analysis combining the GSTT1 and GSTM1 genotypes were also carried out. Subjects with null genotypes for both GSTM1 and GSTT1 were at a significant higher risk for developing asthma (OR = 2.15, 95% CI: 1.39-3.33) compared with subjects who had both active genes. The trend in risk associated with zero, one and two putative high-risk genotypes was significant (chi2 = 12.07, df= 1, p = 0.0005). Overall, our present meta-analysis revealed that the null genotypes of GSTM1 and GSTT1 are associated with risk of asthma in adults especially in non-smoker ones. It might be suggested that chronic smoking carries such a high dose of toxins into the body that overloads the capacity of either GSTM1 or GSTT1 detoxification system. It seems that the GSTM1 and GSTT1 lack their protective values against development of asthma in adults with positive history of smoking. Present results also suggested that there is an additive effect for GSTT1 and GSTM1 genotypes.