Early-Life Environmental Factors, IFN-[gamma] Methylation Patterns, and Childhood Allergic Rhinitis

Background: While early-life risk factors are known to influence the risk of allergies, the biological mechanisms underlying this observation are unclear. The aim of this study was to examine whether DNA methylation in childhood could underlie the association between early-life risk factors and allergic rhinitis (AR). Methods: In total, 234 patients, aged 6 years, were recruited, i.e., 114 were patients with AR (AR group) and 120 healthy children without AR (NAR group). The DNA methylation patterns of the IFN-[gamma] promoter regions in CD4+ cells were analyzed using bisulfite sequencing. The percentage of Th1 was investigated by flow cytometry. The relationship among DNA methylation, early-life environment, and AR was examined. Results: After adjusting for several likely confounders, there was a higher likelihood of AR in children who had mothers with allergies than in children who had nonallergic mothers (OR = 5.19; 95% CI 1.18-29.41), in children who were born in autumn or winter than in children who were born in the summer or spring (OR = 2.69; 95% CI 1.34-5.40), and in children who lived with indoor carpet or wallpaper than in children who lived without indoor carpet or wallpaper (OR = 4.14; 95% CI 2.05-8.30). Compared to the NAR group, the AR group had higher mean methylation levels of the promoter region in IFN-[gamma]Y, and lower numbers of IFN-[gamma]+CD4+ cells were associated with autumn-winter birthdates. The season of birth had an indirect effect on AR at 6 years, which was mediated by the mean IFN-[gamma] promoter methylation level. Conclusions: This study suggests that early-life environments affect AR, and this is supported by the finding of IFN-[gamma]Y methylation as a mediator of the effect of an individual's season of birth on AR. Keywords: Children, Allergic rhinitis, Early-life environment, Methylation, IFN-[gamma]