Association of GSTP1, GSTM1, and GSTT1 polymorphisms with Diisocyanate-induced asthma in Iraqi Arab male workers

Occupational asthma (OA), particularly diisocyanate-induced asthma (DA), is a common work-related respiratory condition. Genetic variations in antioxidant enzyme genes, such as glutathione S-transferases (GSTs), may influence susceptibility to OA. This study investigates associations between polymorphisms in GSTM1, GSTT1, and GSTP1 (rs1695, rs1138272) and DA risk in an Iraqi Arab male population.

A total of 235 male workers exposed to diisocyanates were enrolled: 125 with DA and 110 exposed but asymptomatic controls. Genotyping was performed using multiplex-PCR and RFLP-PCR. Associations were analyzed under various genetic models, including combined genotypes.

No statistically significant associations were found between individual GSTP1 SNPs and overall DA risk. Combined analysis of variant alleles at both GSTP1 SNPs (rs1695 and rs1138272) suggested a nominal association with increased DA risk (OR = 2.05; 95% CI: 1.02-4.12; p = 0.04; adj. p = 0.24). Carriers of the GSTP1 rs1695 variant combined with the GSTT1-null genotype also showed a nominally increased risk (OR = 2.88; p = 0.04; adj. p = 0.12). Stratification by disease severity indicated that GSTM1-null and GSTT1-null genotypes were approximately twofold more frequent among patients with severe DA compared to controls (OR = 2.20; 95% CI:1.01-4.82; p = 0.04 and OR = 2.22; 95% CI: 1.06-4.67; p = 0.03, respectively).

While individual GST polymorphisms were not significantly associated with DA, certain combined genotypes, particularly those involving GSTP1 and GSTT1, showed nominal associations, and GSTM1-null and GSTT1-null genotypes may contribute to severe DA. This is the first study to assess these associations in an Arab population, providing valuable preliminary data for future occupational asthma research.