昆明地区妊娠糖尿病孕妇网膜下脂肪的全基因组甲基化差异研究 [中文引用][英文引用]

目的 本研究应用甲基化芯片技术研究妊娠糖尿病网膜下脂肪与正常对照组的全基因组甲基化差异，提供妊娠期糖尿病网膜下脂肪全基因组范围内的甲基化差异数据背景，为寻找妊娠糖尿病网膜脂肪基因表达差异原因提供线索。方法 收集3例通过OGTT实验确诊但未经过治疗的妊娠期糖尿病患者和同期3例年龄，孕次产次，孕前BMI与之无差异的健康对照者网膜下脂肪组织，提取总RNA后，采用Illumina Methylation BeadChipchip芯片进行检测，并进行基因甲基化结果进行比较，寻找具有甲基化差异的基因。结果 结果发现两研究组中网膜下脂肪的全基因组DNA甲基化存在差异。妊娠糖尿病组中总共有1298个基因发生了低甲基化，1570个基因发生了高甲基化。这些基因参与了细胞骨架构建，细胞凋亡调控，细胞核内信号转导，糖和脂代谢，炎症反应等。进一步数据分析发现，两组样本在miRNA启动区上位点甲基化变化水平不一致的基因有3个，包括：PSORS1C1，PCDHB13和DKFZp686A1627。在同一CpG岛区域位点甲基化变化水平不一致的基因有7个，在miRNA区域具有甲基化差异的基因有13个。结论 正常对照组与GDM组中基因的甲基化位点和水平存在显著差异，这可能与该基因在组织中表达的蛋白水平在两组中的差异表达密切相关。是否甲基化的差异是导致相应基因表达水平差异的原因还需要深入的研究。未来需要进一步弄清DNA甲基化在网膜下脂肪中对基因表达目标蛋白的调控作用，为妊娠糖尿病的治疗和预防提供线索。

Objective  In order to investigate the pathogenesis of gestational diabetes mellitus (GDM), the differences of genes methylation patterns in omenta adipose tissues between pregnant women with GDM and the normal pregnancies were compared.These data provided the background of methylation patterns in whole genome, which could provide the clues for explaining the discrepancy of gene expression between the two study groups. Method 3cases of omenta adipose tissues in insulin untreated GDM pregnancies diagnosed by oral glucose tolerance test (OGTT) were collected. Meanwhile, the same cases of omenta adipose tissues in normal pregnancies were collected. There was no discrepancy between the two groups , including gestation age, parity and pre-pregnancy BMI. The RNAs of these tissues were extracted, and the gene methylation of these tissues were detected by Illumina Methylation BeadChipchip. The differences of gene expression profiles between GDM and normal controls were analyzed in order to find the possible disease genes. Results There was discrepancy of mathylation pattern in whole genome between the two groups. 1298 genes were hypomethylated and 1570 genes were hypermethylated in GDM group. These genes were involved in many physiological functions such as: cytoskeleton conformation, cell apoptosis, ignal transduction,fat and sugar metabolism and inflammation. Futher data supported that there were different methylation patterns in three genes, PSORS1C1 There are notable CpG methylation differences in omental adipose tissues between GDM and the normal pregnancie, which would be closely relatively with the expression difference of target genes. Whether the discrepancy of methylation pattern was the lead course of the exprssion were needed for further research. The mechanisms of gene methylation on target protein should be elucidated, which could provide the clues for prevention and treatment of GDM.