Epigenome-wide and transcriptome-wide analyses reveal gestational diabetes is associated with alterations in the human leukocyte antigen complex.
Epigenome-wide and transcriptome-wide analyses reveal gestational diabetes is associated with alterations in the human leukocyte antigen complex.
复制标题
DOI：
10.1186/s13148-015-0116-y
复制
发表时间：
2015
影响因子：
5.7
通讯作者：
Michels KB
中科院分区：
文献类型：
--
作者：
Binder AM;LaRocca J;Lesseur C;Marsit CJ;Michels KB
在美国，妊娠糖尿病（GDM）影响约10%的妊娠，并增加后代不良健康后果的风险。这些成人疾病倾向可能是由与GDM相关的胎盘解剖学和分子改变决定的。为了评估胎儿编程的机制方面，我们测量了来自哈佛表观遗传出生队列的41例GDM病例和41例无母体并发症的匹配妊娠的胎盘组织中的全基因组甲基化（Infinium HumanMethylation 450 BeadChips）和表达（Affyphin转录组微阵列）。与GDM状态相关的特异性转录和表观遗传扰动包括主要组织相容性复合体（MHC）区域的改变，这在一个独立的队列中得到了验证，罗得岛儿童健康研究。GDM影响的基因调控中的基因本体富集揭示了差异表达中免疫应答途径的过度表达，反映了MHC区域的这些协调变化。这种差异甲基化和表达可能捕获细胞组成的变化，反映了与GDM相关的胎盘生理变化。我们的研究代表了与GDM相关的转录组和甲基化差异的最大调查，为GDM如何塑造宫内环境提供了全面的见解，这可能对胎儿（重新）编程有影响。本文的在线版本（doi：10.1186/s13148-015-0116-y）包含补充材料，可供授权用户使用。
Gestational diabetes mellitus (GDM) affects approximately 10 % of pregnancies in the United States and increases the risk of adverse health outcomes in the offspring. These adult disease propensities may be set by anatomical and molecular alterations in the placenta associated with GDM. To assess the mechanistic aspects of fetal programming, we measured genome-wide methylation (Infinium HumanMethylation450 BeadChips) and expression (Affymetrix transcriptome microarrays) in placental tissue of 41 GDM cases and 41 matched pregnancies without maternal complications from the Harvard Epigenetic Birth Cohort. Specific transcriptional and epigenetic perturbations associated with GDM status included alterations in the major histocompatibility complex (MHC) region, which were validated in an independent cohort, the Rhode Island Child Health Study. Gene ontology enrichment among gene regulation influenced by GDM revealed an over-representation of immune response pathways among differential expression, reflecting these coordinated changes in the MHC region. This differential methylation and expression may be capturing shifts in cellular composition, reflecting physiological changes in the placenta associated with GDM. Our study represents the largest investigation of transcriptomic and methylomic differences associated with GDM, providing comprehensive insight into how GDM shapes the intrauterine environment, which may have implications for fetal (re)programming. The online version of this article (doi:10.1186/s13148-015-0116-y) contains supplementary material, which is available to authorized users.