Glutathione S-transferase GSTP1 is a susceptibility gene for occupational asthma induced by isocyanates

Background: Polymorphism at the pi class glutathione-S-transferase locus (GSTP1) is associated with allergen-induced asthma and related phenotypes. Objective: We sought to determine whether GSTP1 polymorphism influences susceptibility to asthma induced by toluene diisocyanate (TDI). Methods: The role of GSTP1 was assessed in 131 workers exposed to TDI, 92 with TDI-induced asthma and 39 asymptomatic subjects. The phenotype of the disease was characterized by using detailed clinical history, lung volumes, airway responsiveness to methacholine, and airway responsiveness to TDI. GST genotypes were determined by using PCR-based assays. Results: In patients exposed to TDI for 10 or more years, the frequency of the GSTP1 Val/Val genotype was lower in subjects who had asthma (odds ratio, 0.23; 95% confidence interval, 0.05-1.13; P = .074). Similarly, the frequency of this genotype was significantly lower in subjects with evidence of moderate-to-severe airway hyperresponsiveness to methacholine compared with the frequency in subjects with normal or mild hyperresponsiveness (P = .033). Conclusion: These data suggest that homozygosity for the GSTP1*Val allele confers protection against TDI-induced asthma and airway hyperresponsiveness. This view is supported by the finding that the protective effect increases in proportion to the duration of exposure to TDI.