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Farm exposure and time trends in early childhood may influence DNA methylation in genes related to asthma and allergy

机译：农场暴露和儿童时期的时间趋势可能会影响与哮喘和过敏相关的基因中的DNA甲基化

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Background 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. Methods 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. Results 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-rfit SUPPL10-8). 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). Conclusions 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. ? 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.
机译：背景技术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。表观遗传机制可能通过这些疾病中的环境相互作用促进基因。方法我们研究了农村出生队列PASTURE（对过敏的保护：在农村环境中的研究），以调查（a）哮喘候选基因的表观遗传模式是否总体上受到农场暴露的影响;（b）在生命的最初几年中的变化;以及（c）这些变化是否可能导致哮喘的发展。从脐带血中提取DNA，并在4.5岁时在每个时间点以46个样本收集全血。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测试分析层间差异。结果与非农儿童相比，脐带血中，农民的DNA中ORMDL1和STAT6中的区域甲基化程度较低，而RAD50和IL13中的区域中的甲基化程度较高（最低P值（STAT6）= 0.001）。甲基化随时间的变化发生在15个基因区域（最低P值（IL13）= 1.57-rfit SUPPL10-8）。有趣的是，这些差异集中在与哮喘高度相关的基因（ORMDL家族）和IgE调节（RAD50，IL13和IL4）上，而在T调节基因（FOXP3，RUNX3）上却没有。结论在这项第一项先导研究中，儿童早期在外周血细胞中与哮喘和过敏相关的特定基因中，DNA甲基化模式发生了显着变化，而早期暴露于农场环境似乎会影响不同基因中的甲基化模式。 ？ 2013 John Wiley＆Sons A / S。由布莱克韦尔出版有限公司出版。

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