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妊娠期糖尿病患者母血与脐血的全基因组DNA甲基化变异

Genome-wide DNA methylation variation in maternal and cord blood of gestational diabetes population.

作者信息

Kang Jessica, Lee Chien-Nan, Li Hung-Yuan, Hsu Kai-Han, Lin Shin-Yu

机构信息

Department of Obstetrics and Gynecology, National Taiwan University Hospital, No. 8 Chung-Shan South Road, Taipei 100, Taiwan.

Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei 100, Taiwan.

出版信息

Diabetes Res Clin Pract. 2017 Oct;132:127-136. doi: 10.1016/j.diabres.2017.07.034. Epub 2017 Aug 9.

Abstract

AIMS

Gestational diabetes mellitus (GDM) has always been a concerning issue for pregnant women. In recent studies, GDM was found to be related to epigenetic modifications, which would alter gene expressions, thus affecting the patients' and their offspring's health, leading to a higher probability of developing metabolic syndromes and diabetes later in life.

METHODS

In this study, we collected both maternal and cord blood samples from 16 pregnant women and their newborns, including eight exposed to GDM. GDM was diagnosed via a 75g oral glucose tolerance test (OGTT) at 24-28weeks of pregnancy. DNA methylation was measured at 841,573 CpG sites via the Infinium HumanMethylationEPIC BeadChip. An Ingenuity Pathway Analysis was conducted afterwards to identify genes and pathways epigenetically affected by GDM.

RESULTS

We identified the top 200 loci and their corresponding genes in the maternal blood group (n=151) and cord blood group (n=167), both of which were methylated differently in the GDM and unexposed group. Metabolic disease-related pathways and molecules, such as interleukin-6 and interleukin-10 were identified in both groups. These results suggested that GDM has epigenetic effects on both mother and their offspring, which might result in future metabolic syndromes or diabetes.

CONCLUSIONS

The high-throughput platform enabled us to analyze methylation sites throughout the genome and identify the most promising genes and pathways associated with GDM.

摘要

目的

妊娠期糖尿病(GDM)一直是孕妇关注的问题。在最近的研究中,发现GDM与表观遗传修饰有关,表观遗传修饰会改变基因表达,从而影响患者及其后代的健康,导致日后患代谢综合征和糖尿病的可能性更高。

方法

在本研究中,我们收集了16名孕妇及其新生儿的母血和脐带血样本,其中包括8名患有GDM的孕妇。在妊娠24 - 28周时通过75g口服葡萄糖耐量试验(OGTT)诊断GDM。通过Infinium HumanMethylationEPIC BeadChip在841,573个CpG位点测量DNA甲基化。随后进行了 Ingenuity 通路分析,以确定受GDM表观遗传影响的基因和通路。

结果

我们确定了母血组(n = 151)和脐带血组(n = 167)中的前200个位点及其相应基因,在GDM组和未暴露组中,这两组的甲基化情况均有所不同。在两组中都鉴定出了与代谢疾病相关的通路和分子,如白细胞介素 - 6和白细胞介素 - 10。这些结果表明,GDM对母亲及其后代都有表观遗传影响,这可能会导致未来的代谢综合征或糖尿病。

结论

高通量平台使我们能够分析整个基因组中的甲基化位点,并确定与GDM相关的最有前景的基因和通路。

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