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The genetic factors may modify the individual susceptibility to the development of asbestosis. This study investigated whether MnSOD, ECSOD, CAT, iNOS, GSTM1, GSTT1 and GSTP1 genetic polymorphisms represent risk factors for asbestosis in workers occupationally exposed to asbestos.
Methods
The nested case-control study included 262 cases with asbestosis and 265 controls with no asbestos-related disease. Data on cumulative asbestos exposure and smoking were available for all subjects. PCR based methods were used to genotype MnSOD Ala –9Val, ECSOD Arg213Gly, CAT –262C>T, iNOS (CCTTT)n, GSTM1-null, GSTT1-null, GSTP1 Ile105Val and Ala114Val polymorphisms. To asses asbestosis risk, logistic regression analysis was used.
Results
The OR of asbestosis was 3.21 (95%CI 2.43–4.23) for cumulative asbestos exposure; 0.98 (95%CI 0.69–1.39) for smoking; 1.50 (95%CI 1.01–2.24) for MnSOD –9Ala/Ala versus Ala/Val and Val/Val; 1.63 (95%CI 0.62–4.27) for ECSOD 213Arg/Gly versus Arg/Arg; 1.36 (95%CI 0.70–2.62) for CAT –262TT versus CT and CC; 1.20 (95%CI 0.85–1.69) for iNOS LL versus SL and SS; 1.01 (95%CI 0.71–1.43) for GSTM1-null; 0.61 (95%CI 0.40–0.94) for GSTT1-null; 1.52 (95%CI 1.08–2.15) for GSTP1 105Ile/Ile versus 105Ile/Val and 105Val/Val; and 0.97 (95%CI 0.64–1.48) for GSTP1 114Ala/Ala versus 114Ala/Val and 114Val/Val. The associations between MnSOD Ala –9Val polymorphism and asbestosis, and between iNOS (CCTTT)n and asbestosis were modified by CAT –262C>T polymorphism (p=0.038; p=0.031, respectively).
Discussion
This study showed that MnSOD –9Ala/Ala and GSTP1105Ile/Ile genotypes significantly increase the risk of developing asbestosis, while a protective effect was observed for GSTT1-null genotype. A strong interaction was found between MnSOD Ala –9Val and CAT –262C>T, as well as between iNOS (CCTTT)n and CAT –262>T polymorphisms. The findings suggest that, in addition to asbestos exposure, the genetic factors may have a significant influence on developing asbestosis.