Association of and Null Genotypes with Toluene Diisocyanate-Induced Asthma.

Background: Toluene diisocyanate (TDI) causes occupational asthma by generating oxidative stress, leading to tissue injury and inflammation. Glutathione transferases (GSTs) are detoxifying enzymes that eliminate oxidative stress. We examined whether the genotypes of the and genes are associated with TDI-induced occupational asthma (TDI-OA).

Methods: The study population consisted of 26 asthmatics with a positive response to the TDI challenge (TDI-PA) and 27 asthmatics with negative responses (TDI-NA). and null and wild-type genotypes were determined using multiplex PCR. The plasma GSTM1 and GSTT1 protein concentrations were determined using ELISA.

Results: The null genotype was more frequent in the TDI-PA than in the TDI-NA (77.8 . 50.0%, OR = 3.5, =0.03), while the frequency of the null genotype tended to be higher in the TDI-PA than in the TDI-NA (59.3 . 42.3%, OR = 1.98, =0.21). When analyzed together, the / null genotype was more frequent in the TDI-PA than in the TDI-NA (48.2 . 15.3%, OR = 6.5, =0.04). The decline in the FEV in 1 s after TDI challenge was higher with the / null than the wild-type/ null genotypes (24.29% . 7.47%, =0.02). The plasma GSTM1 level was lower with the null than with the wild-type genotypes both before (13.7 . 16.6 ng/mg, =0.04) and after (12.9 . 17.1 ng/mg, =0.007) the TDI challenge, while the GSTT1 level was not changed with either the null or wild-type genotype.

Conclusions: The null genotype, but not alone, may confer susceptibility to TDI-OA. However, the genetic effect of the null genotype may be enhanced synergistically by the null genotype. The genetic effect of was validated in the plasma as the GSTM1 protein level. Therefore, the and genotypes may be useful diagnostic markers for TDI-OA.