Second‐hand smoke and NFE2L2 genotype interaction increases paediatric asthma risk and severity

Abstract

Background: Second-hand smoke (SHS) exposure is associated with paediatric asthma, and oxidative stress is believed to play a role in mediating this association.The nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) is important for the defence against oxidative stress.Objective: To explore interactions between NFE2L2 genotype and SHS exposure in paediatric asthma risk. Methods:We used a genotyped subset of patients of European ancestry (N = 669, median age at enrolment = 6.8 years) enrolled in the clinical cohort Greater Cincinnati Pediatric Clinic Repository as the study population, and a population-based paediatric cohort (N = 791) to replicate our findings. History of asthma diagnosis was obtained from medical records, and SHS exposure was obtained from questionnaires. Four NFE2L2 tagging SNPs were included in the analysis, and interactions between SHS and NFE2L2 genotype were evaluated using logistic regression.Results: Three of the analysed SNPs, rs10183914, rs1806649 and rs2886161, interacted significantly with SHS exposure to increase asthma risk (p ≤ .02). The interaction was replicated in an independent cohort for rs10183914 (p = .04). Interactions between SHS exposure and NFE2L2 genotype were also associated with an increased risk of hospitalization (p = .016). In stratified analyses, NFE2L2 genotype was associated with daily asthma symptoms in children with SHS exposure (OR = 3.1; p = .048).No association was found in children without SHS exposure. Examination of publicly available chromatin immunoprecipitation followed by sequencing (ChIP-seq) data sets confirmed the presence of active histone marks and binding sites for particular transcription factors overlapping the coordinates for the significantly associated SNPs. Conclusions and Clinical Relevance:Our study provides evidence that NFE2L2 genotype interacts with SHS exposure to affect both asthma risk and severity in children and identifies a population of children at increased risk of asthma development.

Association between Secondhand Smoke and Allergic Diseases in Korean Adolescents: Cross-Sectional Analysis of the 2019 KYRBS

“…The participants with allergic disease who were exposed more to SHS in schools and public places were more prevalent than those with allergic diseases who were not exposed to SHS in public. These results are consistent with those of previous studies that have suggested that exposure to SHS is associated with allergic diseases [ 18 , 19 ]. According to the KYRBS, the rate of exposure to SHS in schools increased from 20.0% in 2018 to 21.6% in 2019, and that in public places increased from 51.4% in 2018 to 52.5% in 2019 [ 14 ].…”

Gene‐environment interactions in childhood asthma revisited; expanding the interaction concept

“…Environment‐related factors have had the leading role in the GxE investigations (mainly air pollution and tobacco smoke) with a clear underrepresentation of host characteristics (Table 1), despite their implication in the modification of the genetic risk to develop different asthma‐related traits (Figure 1). 26,32 …”

“…29,30 Additionally, the exploration of gene interactions with early-life environmental exposure to tobacco smoke in asthma susceptibility remains the most studied setting (Table 1). As a result, these studies have suggested interaction effects of known asthma genes with environmental tobacco smoke exposure during childhood (IL1RN, NFE2L2), 31,32 and a novel locus for asthma susceptibility (NAT1) 33 (Table 2). Furthermore, the association of in utero exposure with genetic variants in asthma has been evaluated.…”

Multi-Omics Profiling Approach to Asthma: An Evolving Paradigm

“…Solid evidence exists for the association between childhood asthma risk and exposure to secondhand smoke (SHS) both pre-and postnatally [146,147]. Moreover, SHS has been found to interact with genetic factors to increase asthma risk [148][149][150]. Exposures to environmental microbial communities are believed to have a profound influence on the developing immune system.…”