PURPOSE: Oxidative stress has been suggested to play an important role in the pathogenesis of occupational chronic bronchitis. Cytochromes P450 1A1 (CYP1A1) and 2E1 (CYP2E1) catalyze the oxidation many carcinogenic and toxic chemicals and the formation of their active oxygen metabolites. Members of the glutathione S-transferase supergene family (GSTM1, GSTT1, GSTP1), catalase (CAT1) and NAD(P)H: quinine oxidoreductase 1 (NQO1) are antioxidant enzymes important in the detoxification of environmental pollutants. In this study, we investigate the possible association of the CYP1A1 2455A/G, the CYP2E1 -1053C/T, the CAT 1 1167 T/C and -262C/T, the NQO1 609 C/T, GSTP1 +313A/G, GSTT1-positive/null, GSTM1-positive/null polymorphisms in the development of occupation chronic bronchitis.
METHODS: The study group consisted of 135 patients with occupation chronic bronchitis and 299 unrelated healthy individuals with the same ethnic origin from Republic Bashkortostan, Russian Federation. Polymorphisms were examined by a PCR-RLFP method. Statistical analysis of the results was carried out with Statistica v. 6.0.
RESULTS: The frequency of C allele -262C/T polymorphism was significantly higher in patients (81.48% compared to control 75.0%, X2=3.99, p=0.05). A single base substitution C/T at position -262 have been found characterized higher expression of the catalase. Thus, catalase C allele significantly increased the risk for developing occupational chronic bronchitis in exposed workers (OR=1.47, 95%CI=1.01-2.14). The frequency of the GG genotype of GSTP1 was significantly higher in patients (9.68% versus to control 1.95%, X2=8.67, p=0.005). The distributions of the CYP1A1, CYP2E1, NQO1, GSTM1 and GSTT1 genotypes were similar in the control and patient groups.
CONCLUSION: In conclusion, both the catalase -262C/T and glutathione S-transferase P1 +313A/G polymorphisms, perhaps, have dramatic role in the pathogenesis of lung diseases, particularly occupational lung disorders.
CLINICAL IMPLICATIONS: An understanding of the candidate genes contribution in the development of occupation chronic bronchitis will lead to improvement strategies to prevent and treat this complex lung disease.
DISCLOSURE: Leysan Akhmadishina, None.