Maternal genome-wide DNA methylation profiling in gestational diabetes shows distinctive disease-associated changes relative to matched healthy pregnancies

Several recent reports have described associations between gestational diabetes (GDM) and changes to the epigenomic landscape where the DNA samples were derived from either cord or placental sources. We employed genome-wide 450K array analysis to determine changes to the epigenome in a unique cohort of maternal blood DNA from 11 pregnant women prior to GDM development relative to matched controls. Hierarchical clustering segregated the samples into 2 distinct clusters comprising GDM and healthy pregnancies. Screening identified 100 CpGs with a mean β-value difference of ≥0.2 between cases and controls. Using stringent criteria, 5 CpGs (within <i>COPS8, PIK3R5, HAAO, CCDC124</i>, and <i>C5orf34</i> genes) demonstrated potentials to be clinical biomarkers as revealed by differential methylation in 8 of 11 women who developed GDM relative to matched controls. We identified, for the first time, maternal methylation changes <i>prior</i> to the onset of GDM that may prove useful as biomarkers for early therapeutic intervention.

近期多项研究报道了妊娠糖尿病（gestational diabetes, GDM）与表观基因组图谱改变之间的关联，此类研究的DNA样本均取自脐带血或胎盘组织。本研究采用全基因组450K芯片分析技术，针对11名GDM发病前孕妇的母体外周血DNA所构成的独特队列，与匹配对照进行对比，以探究其表观基因组的改变情况。层次聚类将样本划分为两个独立的簇，分别对应GDM组与健康妊娠组。经筛选得到100个CpG位点，病例组与对照组的平均β值差异≥0.2。通过严格筛选标准，位于<COPS8>、<PIK3R5>、<HAAO>、<CCDC124>及<C5orf34>基因内的5个CpG位点具备成为临床生物标志物的潜力：在11名后续发展为GDM的孕妇中，有8名的该类位点相较于匹配对照呈现出显著差异甲基化特征。本研究首次鉴定出GDM发病前的母体甲基化改变，此类改变或可作为早期治疗干预的生物标志物，具备实际应用价值。