Gene-Environment Interaction between the IL1RN Variants and Childhood Environmental Tobacco Smoke Exposure in Asthma Risk.

Yongzhao Shao,Meng Qian,Yian Zhang,Mengling Liu,Joan Reibman,Maria-Elena Fernandez-Beros

doi:10.3390/ijerph17062036

Abstract

(1) Background: Variants of the interleukin-1 receptor antagonist (IL1RN) gene, encoding an anti-inflammatory cytokine, are associated with asthma. Asthma is a chronic inflammatory disease of the airway influenced by interactions between genetic variants and environmental factors. We discovered a gene–environment interaction (GEI) of IL1RN polymorphisms with childhood environmental tobacco smoke (ETS) exposure on asthma susceptibility in an urban adult population. (2) Methods: DNA samples from the NYU/Bellevue Asthma Registry were genotyped for tag SNPs in IL1RN in asthma cases and unrelated healthy controls. Logistic regressions were used to study the GEI between IL1RN variants and childhood ETS exposures on asthma and early onset asthma, respectively, adjusting for population admixture and other covariates. (3) Results: Whereas the rare genotypes of IL1RN SNPs (e.g., GG in SNP rs2234678) were associated with decreased risk for asthma among those without ETS exposure (odds ratio OR = 0.215, p = 0.021), they are associated with increased risk for early onset asthma among those with childhood ETS (OR = 4.467, p = 0.021). (4) Conclusions: We identified a GEI between polymorphisms of IL1RN and childhood ETS exposure in asthma. Analysis of GEI indicated that childhood ETS exposure disrupted the protective effect of some haplotypes/genotypes of IL1RN for asthma and turned them into high-risk polymorphisms for early onset asthma.

Highlights

Asthma is a chronic inflammatory lung disease with a large global burden [1,2,3]
Ramadas et al showed that the rare genotype GG at single nucleotide polymorphisms (SNPs) rs2234678 carried a significant risk for asthma in children less than 10 years old with exposure to maternal smoking during pregnancy [14], we examined the interaction between interleukin-1 receptor antagonist (IL1RN) genotypes and childhood Environmental tobacco smoke (ETS) exposure on the risk of early onset asthma in the NYUBAR
Our analyses indicated that these protective effects of these tag SNP polymorphisms were significant only within the groups without childhood ETS exposure and these polymorphisms became risk variants for early onset asthma in the subgroup exposed to childhood ETS

Summary

Introduction

Asthma is a chronic inflammatory lung disease with a large global burden [1,2,3]. A complex genetic disorder, asthma results from the interplay of multiple genetic variants with environmental factors [4,5,6,7]. Numerous genes associated with asthma susceptibility have been identified through candidate gene analyses and genome-wide linkage or association studies [7,8]. Members of the IL1 family participate in inflammation with well-established biological plausibility for an association between IL1 family genes and asthma or related phenotypes [16,17,18,19].

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Discussion

Conclusion