Glutathione S-transferases T1 and M1 and asthma risk in 10,000 individuals and in meta-analysis

Background: We tested the hypothesis that genetically reduced activity of glutathione S -transferases (GST) T1 and M1 were associated with increased risk for asthma. Methods: We genotyped participants in the Copenhagen City Heart Study (n=10,335) for the exact number of GSTT1 and GSTM1 gene copies and recorded asthma outcomes. We also performed a meta-analysis of 37 studies comprising 5954 asthma cases and 14513 controls to assess the risk for asthma in GSTT1*0/0 homozygotes. Results: The odds ratio for asthma was stepwise increased with decreasing number of GSTT1 gene copies (P=0.03): GSTT1*0/0 homozygotes and *1/0 heterozygotes had adjusted odds ratios for asthma of 1.27 (95%CI: 1.03-1.56) and 1.07 (0.92-1.25), respectively, compared with *1/1 homozygotes. When the asthma definition was restricted to participants who only had allergic asthma or took asthma medication, GSTT1*0/0 versus *1/1 homozygotes had adjusted odds ratios of 1.34 (1.01-1.79) for allergic asthma and of 1.20 (0.88-1.64) for asthma medication. When the asthma definition included any of the three different asthma definitions, GSTT1*0/0 homozygotes had an adjusted odds ratio for any asthma of 1.24 (1.02-1.51) compared with *1/1 homozygotes. In meta-analysis, random effects odds ratio for asthma was increased at 1.35 (1.14-1.59) in GSTT1*0/0 homozygotes versus individuals with *1/0 or *1/1 genotypes. None of the risk estimates for GSTM1 genotypes differed from 1.0 for any of the four different definitions of asthma (P=0.17-0.95). Conclusion: The results suggest that individuals with genetic GSTT1 deficiency have increased risk for asthma, while asthma risk is unaffected by GSTM1 deficiency.