Abstract
BackgroundRecent research has pointed out the important roles of epigenetic modifications in the development and persistence of allergic rhinitis (AR), especially in relation to DNA methylation of disease-associated genes. We investigated whether AR susceptibility genes were epigenetically regulated, and whether methylation modulation of these genes in response to early-life environment could be a molecular mechanism underlying the risk for AR onset in a cohort of children aged 3–6 years in China.MethodsPeripheral blood mononuclear cell (PBMC) samples were collected from 130 children patients, aged 3–6 years and diagnosed with AR; and 154 matched controls to detect promoter methylation in 25 AR susceptibility genes with the MethylTarget approach. Methylation levels were compared for each CpG site, each amplified region, and each gene. In addition, the relationship among DNA methylation, early-life environmental risk factors and AR onset were assessed.ResultsMaternal allergic history (P = 0.0390) and pet exposure (P = 0.0339) were significantly associated with increased 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 hypomethylation of ADAM33 was significantly associated with higher 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 with methylation level of ADAM33 increased the risk for AR onset 1.423 times more in children (95% CI = 0.0290–4.109, P-value = 0.005).ConclusionThis study provides evidence that early-life pet exposure and low methylation level of ADAM33 increase AR risk in children, and the interaction between pet exposure and methylation level of ADAM33 may play an important role in the development of AR.
Highlights
Recent research has pointed out the important roles of epigenetic modifications in the development and persistence of allergic rhinitis (AR), especially in relation to DNA methylation of disease-associated genes
No effects were found on season of birth or exposure to second-hand smoke for AR risk
The aim of the study was to investigate the relationship among environmental risk factors, the methylation level of AR candidate genes reported from polymorphism association studies and AR risk in a cohort of children aged 3–6 years in China
Summary
Recent research has pointed out the important roles of epigenetic modifications in the development and persistence of allergic rhinitis (AR), especially in relation to DNA methylation of disease-associated genes. AR is a multifactorial disease triggered by genetic and environmental factors as well as their interaction. Considering the dramatic increase in the prevalence of AR [6], the epigenetic modification may be an important genetic factor to better understand the environmental effects on allergic diseases. DNA methylation, which refers to the addition of a methyl group to DNA, plays a crucial role in controlling the gene expression patterns. Zhang et al have modeled differences between genomewide DNA methylation and allergic sensitization during adolescence. Methylation modulation of several candidate genes has been reported to have an important role in AR development [9]
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