Relationship between air pollution, NFE2L2 gene polymorphisms and childhood asthma in a Hungarian population

Abstract

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)00.290, p00.0015, and OR00.437, p0 0.007, respectively). Furthermore, case-only analyses revealed significant differences for these SNPs between asthma patients that lived in modestly or highly polluted environment , p 00.01, and OR 0 0.51, p00.02, 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.

Genome-wide association study of infectious bovine keratoconjunctivitis in Angus cattle

“…Wangy et al indicated that NFE2L2 was an essential transcription factor in protecting living organisms from oxidative stress-related disease. Ungvari et al [35] showed that polymorphisms in the regulatory regions of NFE2L2 are associated with susceptibility to infection-induced asthma in the study of relationship between air pollution, NFE2L2 gene polymorphisms and childhood asthma in a Hungarian population. They also found remarkable differences in the genotype distributions of these polymorphisms between different polluted regions, which indicate an environment-dependent regulation of the antioxidant defense mechanisms.…”

Aryl hydrocarbon receptor activation by diesel exhaust particles mediates epithelium‐derived cytokines expression in severe allergic asthma

“…These levels are above the permissible level of 15 μg/m 3 by the National Air Quality Standard of Taiwan. The response to environmental pollution may be genetically influenced by factors such as nuclear factor erythroid‐derived 2‐like 2 (NFE2L2, also known as Nrf2) and its negative regulator protein Kelch‐like ECH‐associated protein 1 (KEAP1) . These genes have been reported to be involved in the regulation of antioxidant oxidative stress, airway inflammation, as well as Th2 cytokine release …”

Genetic polymorphism of the Nrf2 promoter region is associated with vitiligo risk in Han Chinese populations

“…Nrf2 rs6721961 G/T polymorphism is located at position −617 of the promoter region, affecting the ARE binding site and possibly gene expression. Nrf2 functional polymorphisms have been linked to the risk of developing ALI after major trauma , childhood asthma caused by air pollution , and oxidative stress‐related defects in human spermatogenesis caused by heavy smoking . In addition, in one study of forearm vasodilatory responses, Caucasian subjects with the Nrf2 rs6721961 T allele had decreased blood flow and increased vascular resistance as compared to that in non‐carriers, while no such association was observed among African‐American subjects , suggesting an ethnic component to the distribution of the Nrf2 rs6721961 G/T polymorphism.…”