Li Youjin, Rui Xiaoqing, Ma Beiying, Jiang Fan, Chen Jie
Department of Otorhinolaryngology-Head & Neck Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China,
Department of Otorhinolaryngology-Head & Neck Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Int Arch Allergy Immunol. 2019;178(4):323-332. doi: 10.1159/000495304. Epub 2019 Jan 4.
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).
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-γ 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.
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-γY, and lower numbers of IFN-γ+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-γ promoter methylation level.
This study suggests that early-life environments affect AR, and this is supported by the finding of IFN-γY methylation as a mediator of the effect of an individual's season of birth on AR.
虽然已知早期生活风险因素会影响过敏风险，但这一现象背后的生物学机制尚不清楚。本研究的目的是探讨儿童期DNA甲基化是否可能是早期生活风险因素与变应性鼻炎（AR）之间关联的基础。
共招募了234名6岁患者，即114名AR患者（AR组）和120名无AR的健康儿童（非AR组）。采用亚硫酸氢盐测序法分析CD4+细胞中IFN-γ启动子区域的DNA甲基化模式。通过流式细胞术检测Th1的百分比。研究了DNA甲基化、早期生活环境与AR之间的关系。
在调整了几个可能的混杂因素后，母亲患有过敏的儿童患AR的可能性高于母亲无过敏的儿童（OR = 5.19；95%CI 1.18 - 29.41），秋季或冬季出生的儿童患AR的可能性高于夏季或春季出生的儿童（OR = 2.69；95%CI 1.34 - 5.40），居住在有室内地毯或壁纸环境中的儿童患AR的可能性高于无室内地毯或壁纸环境中的儿童（OR = 4.14；95%CI 2.05 - 8.30）。与非AR组相比，AR组IFN-γY启动子区域的平均甲基化水平更高，且IFN-γ+CD4+细胞数量减少与秋冬出生有关。出生季节对6岁儿童的AR有间接影响，这是由IFN-γ启动子平均甲基化水平介导的。
本研究表明，早期生活环境会影响AR，IFN-γY甲基化作为个体出生季节对AR影响的介导因素这一发现支持了这一点。
