Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany.
Allergy. 2013 Mar;68(3):355-64. doi: 10.1111/all.12097. Epub 2013 Jan 25.
Genetic susceptibility and environmental influences are important contributors to the development of asthma and atopic diseases. Epigenetic mechanisms may facilitate gene by environment interactions in these diseases.
We studied the rural birth cohort PASTURE (Protection against allergy: study in rural environments) to investigate (a) whether epigenetic patterns in asthma candidate genes are influenced by farm exposure in general, (b) change over the first years of life, and (c) whether these changes may contribute to the development of asthma. DNA was extracted from cord blood and whole blood collected at the age of 4.5 years in 46 samples per time point. DNA methylation in 23 regions in ten candidate genes (ORMDL1, ORMDL2, ORMDL3, CHI3L1, RAD50, IL13, IL4, STAT6, FOXP3, and RUNX3) was assessed by pyrosequencing, and differences between strata were analyzed by nonparametric Wilcoxon-Mann-Whitney tests.
In cord blood, regions in ORMDL1 and STAT6 were hypomethylated in DNA from farmers' as compared to nonfarmers' children, while regions in RAD50 and IL13 were hypermethylated (lowest P-value (STAT6) = 0.001). Changes in methylation over time occurred in 15 gene regions (lowest P-value (IL13) = 1.57*10(-8)). Interestingly, these differences clustered in the genes highly associated with asthma (ORMDL family) and IgE regulation (RAD50, IL13, and IL4), but not in the T-regulatory genes (FOXP3, RUNX3).
In this first pilot study, DNA methylation patterns change significantly in early childhood in specific asthma- and allergy-related genes in peripheral blood cells, and early exposure to farm environment seems to influence methylation patterns in distinct genes.
遗传易感性和环境影响是哮喘和特应性疾病发展的重要因素。表观遗传机制可能有助于这些疾病中的基因与环境相互作用。
我们研究了农村出生队列 PASTURE（防止过敏：农村环境研究），以调查：（a）哮喘候选基因中的表观遗传模式是否受到一般农场暴露的影响；（b）生命最初几年的变化；以及（c）这些变化是否可能导致哮喘的发展。从脐带血和 4.5 岁时的全血中提取 DNA，每个时间点采集 46 个样本。通过焦磷酸测序评估十个候选基因（ORMDL1、ORMDL2、ORMDL3、CHI3L1、RAD50、IL13、IL4、STAT6、FOXP3 和 RUNX3）中 23 个区域的 DNA 甲基化，并通过非参数 Wilcoxon-Mann-Whitney 检验分析分层之间的差异。
在脐带血中，与非农民儿童相比，农民儿童的 ORMDL1 和 STAT6 基因中的区域呈低甲基化，而 RAD50 和 IL13 基因中的区域呈高甲基化（最低 P 值（STAT6）= 0.001）。随着时间的推移，15 个基因区域的甲基化发生了变化（最低 P 值（IL13）= 1.57*10(-8)）。有趣的是，这些差异聚集在与哮喘（ORMDL 家族）和 IgE 调节（RAD50、IL13 和 IL4）高度相关的基因中，但不在 T 调节基因（FOXP3、RUNX3）中。
在这项首次试点研究中，外周血单个核细胞中特定哮喘和过敏相关基因的 DNA 甲基化模式在儿童早期发生显著变化，早期暴露于农场环境似乎会影响不同基因的甲基化模式。
