Gene-Environment Interaction between the <i>IL1RN</i> Variants and Childhood Environmental Tobacco Smoke Exposure in Asthma Risk

• Main Authors: Yongzhao Shao, Yian Zhang, Mengling Liu, Maria-Elena Fernandez-Beros, Meng Qian, Joan Reibman
• Format: Article
• Language: English
• Published: MDPI AG 2020-03-01
• Series: International Journal of Environmental Research and Public Health
• Subjects: gene and environment interaction; environmental tobacco smoke; <i>il1rn</i> variants; early onset asthma; snp genotypes; risk haplotypes; case-control association study; population admixture; ancestral informative markers; inflammation
• Online Access: https://www.mdpi.com/1660-4601/17/6/2036

(1) Background: Variants of the interleukin-1 receptor antagonist (<i>IL1RN</i>) 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&#8722;environment interaction (GEI) of <i>IL1RN</i> 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 <i>IL1RN</i> in asthma cases and unrelated healthy controls. Logistic regressions were used to study the GEI between <i>IL1RN</i> 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 <i>IL1RN</i> 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 <i>IL1RN</i> and childhood ETS exposure in asthma. Analysis of GEI indicated that childhood ETS exposure disrupted the protective effect of some haplotypes/genotypes of <i>IL1RN</i> for asthma and turned them into high-risk polymorphisms for early onset asthma.