CYP1A1, CYP1A2 and CYBA gene polymorphisms associated with oxidative stress in COPD

Abstract: Background: The genetic susceptibility to chronic obstructive pulmonary disease (COPD) depends on detoxification and antioxidant enzymes, which detoxify cigarette smoke reactive components that, otherwise, generate oxidative stress. Methods: In a case–control study of 346 subjects with and without COPD, we examined the polymorphisms 462Ile/Val, 3801T/C of CYP1A1, −3860G/A of CYP1A2 and −930A/G, 242C/T of CYBA individually or in combination and their contribution to oxidative stress markers by measuring malondialdehyde (MDA), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx). Results: COPD patients had significantly increased MDA concentration (p <0.001) and decreased CAT activity, GSH concentration, GPx activity (p ≤0.01). The patients were over-represented by the alleles 462Val, 3801C of CYP1A1 and −930G, 242C of CYBA (p <0.001, p =0.003, p =0.030 and p =0.031, respectively) and consequently the haplotypes of same alleles i.e. 462Val:3801C, 462Val:3801T and −930G:242C (p =0.048, p =0.016 and p =0.039, respectively). Similarly, CYP1A1 and CYP1A2 haplotypes, 462Val:3860G and 462Val:3801T:3860G were significantly over-represented (p =0.001 and p =0.003), respectively in patients. The same alleles-associated genotype-combinations between genes were more prevalent in patients. Of note, the genotypes, 462Ile/Val+Val/Val, 3801TC+CC of CYP1A1 and −930AG+GG of CYBA associated with increased MDA concentration (p =0.018, p =0.045 and p =0.017, respectively), decreased CAT activity (p <0.0001, p =0.080 and p <0.0001, respectively) and GSH concentration (p <0.0001, p =0.0002 and p =0.011, respectively) in patients. Conclusion: The identified alleles, its haplotypes and the genotype-combination along with increased oxidative stress, signify the importance in susceptibility to COPD. [Copyright &y& Elsevier]