Maternal gestational diabetes is associated with genome-wide DNA methylation variation in placenta and cord blood of exposed offspring
Maternal gestational diabetes is associated with genome-wide DNA methylation variation in placenta and cord blood of exposed offspring
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DOI：
10.1093/hmg/ddv013
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发表时间：
2015-06-01
影响因子：
3.5
通讯作者：
Hitman, Graham A.
中科院分区：
文献类型：
--
作者：
Finer, Sarah;Mathews, Chris;Hitman, Graham A.
已证明，发育中的胎儿暴露于母体妊娠期糖尿病（GDM）可规划未来患糖尿病和肥胖症的风险。胎儿组织中的表观遗传变异可能通过妊娠环境与基因功能的相互作用在代谢性疾病规划中起机械作用。我们的目的是确定全基因组DNA甲基化变异的脐带血和胎盘所生的后代，母亲有和没有GDM。对南亚裔孕妇进行了研究，并在足月分娩时对胎儿组织进行了采样。使用Illumina HumanMethylation450 BeadChip检测27例GDM暴露和21例未暴露后代的胎盘和脐带血中全基因组DNA甲基化。我们鉴定了1485个脐带血和1708个胎盘甲基化可变位置（MVP），实现了全基因组显著性（校正P值< 0.05），甲基化差异> 5%。MVP不成比例地位于第一外显子内。使用生物信息学共甲基化算法来检测在74%的胎盘和59%的脐带血MVP处观察到的每个MVP周围的IOOObp窗口中的一致的甲基化方向性。KEGG途径分析显示，参与内吞作用，MAPK信号转导和细胞外触发细胞内代谢过程的途径丰富。复制研究应将基因组学和转录组学与纵向采样相结合，以阐明稳定性，确定转化为生物标志物和预防研究的因果关系。
Exposure of a developing foetus to maternal gestational diabetes (GDM) has been shown to programme future risk of diabetes and obesity. Epigenetic variation in foetal tissue may have a mechanistic role in metabolic disease programming through interaction of the pregnancy environment with gene function. We aimed to identify genome-wide DNA methylation variation in cord blood and placenta from offspring born to mothers with and without GDM. Pregnant women of South Asian origin were studied and foetal tissues sampled at term delivery. The Illumina HumanMethylation450 BeadChip was used to assay genome-wide DNA methylation in placenta and cord blood from 27 GDM exposed and 21 unexposed offspring. We identified 1485 cord blood and 1708 placenta methylation variable positions (MVPs) achieving genome-wide significance (adjusted P-value < 0.05) with methylation differences of > 5%. MVPs were disproportionately located within first exons. A bioinformatic co-methylation algorithm was used to detect consistent directionality of methylation in 1000 bp window around each MVP was observed at 74% of placenta and 59% of cord blood MVPs. KEGG pathway analysis showed enrichment of pathways involved in endocytosis, MAPK signalling and extracellular triggers to intracellular metabolic processes. Replication studies should integrate genomics and transcriptomics with longitudinal sampling to elucidate stability, determine causality for translation into biomarker and prevention studies.