Air pollution and subsequent increased oxidative stress have long been recognized as contributing factors for
asthma phenotypes. Individual susceptibility to oxidative stress is determined by genetic variations of the
antioxidant defence system. In this study, we analysed the association between environmental
nitrogen dioxide (NO(2)) exposure and single nucleotide polymorphisms (SNP) in NFE2L2 and KEAP1 genes and their common impact on
asthma risk. We genotyped 12 SNPs in a case-control study of 307 patients diagnosed with
asthma and 344 controls. NO(2) concentration was collected from the period preceding the development of
asthma symptoms. Multiple logistic regression was applied to evaluate the effects of the studied genetic variations on
asthma outcomes in interaction with NO(2) exposure. Our data showed that genotypes of rs2588882 and rs6721961 in the regulatory regions of the NFE2L2 gene were inversely associated with
infection-induced
asthma (odds ratio (OR) = 0.290, p = 0.0015, and OR = 0.437, p = 0.007, respectively). Furthermore, case-only analyses revealed significant differences for these SNPs between
asthma patients that lived in modestly or highly polluted environment (OR = 0.43 (0.23-0.82), p = 0.01, and OR = 0.51, p = 0.02, respectively, in a dominant model). In conclusion, our results throw some new light upon the impact of NFE2L2 polymorphisms on
infection-induced
asthma risk and their effect in gene-environment interactions.