Interaction between early-life pet exposure and methylation pattern of ADAM33 on Allergic Rhinitis among a cohort of kindergartens in China

Abstract

Background Recent research has pointed out the important role of epigenetic modifications in the development and persistence of Allergic Rhinitis (AR), especially DNA methylation. We investigated whether AR susceptibility genes are epigenetically regulated, and whether methylation modulation of these genes in response to early-life environment could be a molecular mechanism underlying the risk of AR in a cohort of kindergartens in China. Methods Peripheral blood mononuclear cell (PBMCs) samples were collected from 130 kindergarten patients, aged 3–6 years with AR and 154 matched healthy controls to detect promoter methylation in 25 AR susceptibility genes with the MethylTarget approach. Methylation level was compared for each CpG site, each amplified region, and each gene. In addition, the relationship among DNA methylation, early-life environment risk factors and AR were assessed. Results Maternal allergic history (P = 0.0390) and exposure to pet (P = 0.0339) were significantly associated with increase AR risk. Differential methylation analyses were successfully performed for 507 CpG sites, 34 amplified regions and 17 genes and significant hypomethylation was observed in the promoter region of ADAM33 in AR patients [multiple test-corrected (FDR) P-value < 0.05]. Spearman correlation analysis revealed that the hypermethylation of ADAM33 was significantly associated with lower serum total eosinophil counts (Spearman's ρ: -0.187, P-value = 0.037). According to the results of the multiple regression analysis, after adjusting for cofounders, the interaction of early-life pet exposure and methylation level of ADAM33 increased the risk of AR 1.423 times in kindergartens (95% CI = 0.0290–4.109, P-value = 0.005). Conclusion This study provides evidence that early-life pet exposure and low methylation level of ADAM33 increase AR risk in kindergartens, and the interaction between pet exposure and methylation level of ADAM33 may play an important role in the development of AR.