出生季节与DNA甲基化和过敏性疾病的关系
2016/11/09
摘要
背景：出生季节影响过敏风险，但是，这种表象的生物机制目前还不清楚。环境影响DNA甲基化，对基因表达和疾病具有潜在持久的影响。本研究探讨DNA甲基化是否可以揭示出生季节与过敏之间的关联。
方法：对Isle of Wight (IoW)出生队列中18岁的参与者（N = 367）进行了出生季节对过敏性疾病发生风险的评估。测定全血表观基因组范围的DNA甲基化，用培训和测试技术检测与季节相关的CpGs。验证方法检查8岁哮喘的预防和发病率以及螨过敏（PIAMA）队列。对DNA甲基化、出生季节和过敏之间的关系进行了研究。在Isle of Wight (IoW)第三代队列新生儿中分析CpGs。
结果:秋季出生的胎儿相对于春季出生的患湿疹的风险增加。在表观基因组相关研究中，92 CpGs的甲基化显示出与出生季节的相关性。在验证中，偶然发现比预期更多的CpGs具有相同的指向性，四组差异显著。与季节相关的甲基化在与发育、细胞周期和细胞凋亡相关的网络中更丰富。20个CpGs名义上与过敏相关。2个CpGs略与过敏的成因相关。在新生儿中季节相关的甲基化基本不存在，提示这是产后出现的。
结论:这项研究表明，成年期的DNA甲基化与出生的季节有关，支持DNA甲基化可以从机理上解释出生季节对过敏的影响这一假设，虽然其他的机制也可能参与其中。
（苏欣 审校）
Allergy. 2016 Sep;71(9):1314-24. doi: 10.1111/all.12882. Epub 2016 Mar 29.
Association of season of birth with DNA methylation and allergic disease.
Lockett GA1, Soto-Ramírez N2, Ray MA2, Everson TM3, Xu CJ4,5, Patil VK6,7, Terry W2, Kaushal A2, Rezwan FI1, Ewart SL8, Gehring U9, Postma DS10,Koppelman GH11, Arshad SH6,7, Zhang H2, Karmaus W2, Holloway JW1,7.
Author information
Abstract
BACKGROUND:Season of birth influences allergy risk; however, the biological mechanisms underlying this observation are unclear. The environment affects DNA methylation, with potentially long-lasting effects on gene expression and disease. This study examined whether DNA methylation could underlie the association between season of birth and allergy.
METHODS:In a subset of 18-year-old participants from the Isle of Wight (IoW) birth cohort (n = 367), the risks of birth season on allergic outcomes were estimated. Whole blood epigenome-wide DNA methylation was measured, and season-associated CpGs detected using a training-and-testing-based technique. Validation method examined the 8-year-old Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. The relationships between DNA methylation, season of birth and allergy were examined. CpGs were analysed in IoW third-generation cohort newborns.
RESULTS:Autumn birth increased risk of eczema, relative to spring birth. Methylation at 92 CpGs showed association with season of birth in the epigenome-wide association study. In validation, significantly more CpGs had the same directionality than expected by chance, and four were statistically significant. Season-associated methylation was enriched among networks relating to development, the cell cycle and apoptosis. Twenty CpGs were nominally associated with allergic outcomes. Two CpGs were marginally on the causal pathway to allergy. Season-associated methylation was largely absent in newborns, suggesting it arises post-natally.
CONCLUSIONS:This study demonstrates that DNA methylation in adulthood is associated with season of birth, supporting the hypothesis that DNA methylation could mechanistically underlie the effect of season of birth on allergy, although other mechanisms are also likely to be involved.
© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
KEYWORDS:450K array; DNA methylation; epigenetics; epigenome-wide association study; season of birth
Allergy. 2016 Sep;71(9):1314-24. doi: 10.1111/all.12882. Epub 2016 Mar 29.
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