Association of GSTM1 and GSTT1 Null Genotypes with Toluene Diisocyanate-Induced Asthma

Abstract

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 GSTM1 and GSTT1 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). GSTM1 and GSTT1 null and wild-type genotypes were determined using multiplex PCR. The plasma GSTM1 and GSTT1 protein concentrations were determined using ELISA. Results. The GSTM1 null genotype was more frequent in the TDI-PA than in the TDI-NA (77.8 vs. 50.0%, OR = 3.5, p = 0.03 ), while the frequency of the GSTT1 null genotype tended to be higher in the TDI-PA than in the TDI-NA (59.3 vs. 42.3%, OR = 1.98, p = 0.21 ). When analyzed together, the GSTM1/GSTT1 null genotype was more frequent in the TDI-PA than in the TDI-NA (48.2 vs. 15.3%, OR = 6.5, p = 0.04 ). The decline in the FEV in 1 s after TDI challenge was higher with the GSTM1/GSTT1 null than the GSTM1 wild-type/GSTT1 null genotypes (24.29% vs. 7.47%, p = 0.02 ). The plasma GSTM1 level was lower with the GSTM1 null than with the GSTM1 wild-type genotypes both before (13.7 vs. 16.6 ng/mg, p = 0.04 ) and after (12.9 vs. 17.1 ng/mg, p = 0.007 ) the TDI challenge, while the GSTT1 level was not changed with either the GSTT1 null or wild-type genotype. Conclusions. The GSTM1 null genotype, but not GSTT1 alone, may confer susceptibility to TDI-OA. However, the genetic effect of the GSTM1 null genotype may be enhanced synergistically by the GSTT1 null genotype. The genetic effect of GSTM1 was validated in the plasma as the GSTM1 protein level. Therefore, the GSTM1 and GSTT1 genotypes may be useful diagnostic markers for TDI-OA.

The Leucocyte Telomere Length, GSTM1 and GSTT1 Null Genotypes and the Risk of Chronic Obstructive Pulmonary Disease

“…In our study, we found higher prevalence of the GSTM1 null variant and at least one null variant of either GSTM1 or GSTT1 in COPD patients. Based on the experimental studies of Seidegård et al [ 33 ], as well as the results of Lee et al [ 34 ], concerning the effects of the null variant of GSTM1 and GSTT1 genes on enzyme activity and enzyme protein levels, we suggest that the loss of enzymatic activity in COPD patients that carry the null GSTM1 variant results in altered antioxidant defense and the detoxification of ROS and their products. This additionally contributes to the pathological changes present in COPD due to oxidation and inflammation…”

Study on the association of Glutathione S-transferase Mu 1 (GSTM1) gene polymorphism with acute decompensated heart failure with reduced ejection fraction

“…The null polymorphism, which arises in GSTM1due to the complete gene deletion and lack of GST function, has been connected to the development and onset of various illnesses such as psoriasis, atherosclerotic cardiovascular disease (ASCVD), malignancy and type 2 diabetes mellitus (DM2) (Lee et al, 2022; Sobha and Ebenezar 2022). The null genotype polymorphism causes oxidative stress due to the decreased antioxidant capacity, which results in inflammation and other cellular dysfunctions in chronic disorders (Lee et al, 2022). The genotype GSTM1 null is linked to a higher risk of cardiovascular disease (Bhatti et al, 2018).…”