Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Rubloff 12, 420 E. Superior Street, Chicago, IL 60611, USA.
Int J Mol Sci. 2023 Mar 23;24(7):6047. doi: 10.3390/ijms24076047.
Gestational diabetes (GDM) is one of the most common complications of pregnancy, affecting as many as one in six pregnancies. It is associated with both short- and long-term adverse outcomes for the mother and fetus and has important implications for the life course of affected women. Advances in genetics and epigenetics have not only provided new insight into the pathophysiology of GDM but have also provided new approaches to identify women at high risk for progression to postpartum cardiometabolic disease. GDM and type 2 diabetes share similarities in their pathophysiology, suggesting that they also share similarities in their genetic architecture. Candidate gene and genome-wide association studies have identified susceptibility genes that are shared between GDM and type 2 diabetes. Despite these similarities, a much greater effect size for in GDM compared to type 2 diabetes and association of , which encodes a hexokinase, with GDM but not type 2 diabetes suggest some differences in the genetic architecture of GDM. Genetic risk scores have shown some efficacy in identifying women with a history of GDM who will progress to type 2 diabetes. The association of epigenetic changes, including DNA methylation and circulating microRNAs, with GDM has also been examined. Targeted and epigenome-wide approaches have been used to identify DNA methylation in circulating blood cells collected during early, mid-, and late pregnancy that is associated with GDM. DNA methylation in early pregnancy had some ability to identify women who progressed to GDM, while DNA methylation in blood collected at 26-30 weeks gestation improved upon the ability of clinical factors alone to identify women at risk for progression to abnormal glucose tolerance post-partum. Finally, circulating microRNAs and long non-coding RNAs that are present in early or mid-pregnancy and associated with GDM have been identified. MicroRNAs have also proven efficacious in predicting both the development of GDM as well as its long-term cardiometabolic complications. Studies performed to date have demonstrated the potential for genetic and epigenetic technologies to impact clinical care, although much remains to be done.
妊娠期糖尿病（GDM）是最常见的妊娠并发症之一，多达六分之一的妊娠会受到影响。它与母婴的短期和长期不良结局都有关联，并且对受影响女性的生命历程有着重要影响。遗传学和表观遗传学的进步不仅为 GDM 的病理生理学提供了新的见解，也为识别高风险进展为产后心血管代谢疾病的女性提供了新的方法。GDM 和 2 型糖尿病在病理生理学上有相似之处，这表明它们在遗传结构上也有相似之处。候选基因和全基因组关联研究已经确定了 GDM 和 2 型糖尿病共有的易感基因。尽管存在这些相似之处，但 GDM 中的 效应大小明显大于 2 型糖尿病，并且编码己糖激酶的 与 GDM 相关，而与 2 型糖尿病无关，这表明 GDM 的遗传结构存在一些差异。遗传风险评分已显示出在识别有 GDM 病史且将进展为 2 型糖尿病的女性方面具有一定的效果。与 GDM 相关的表观遗传变化，包括 DNA 甲基化和循环 microRNAs，也已被研究。已经使用靶向和全基因组方法来鉴定在妊娠早期、中期和晚期采集的循环血细胞中与 GDM 相关的 DNA 甲基化。妊娠早期的 DNA 甲基化在一定程度上能够识别出进展为 GDM 的女性，而在妊娠 26-30 周采集的血液中的 DNA 甲基化则提高了仅凭临床因素识别产后发生异常葡萄糖耐量风险的女性的能力。最后，鉴定出在妊娠早期或中期存在且与 GDM 相关的循环 microRNAs 和长链非编码 RNA。microRNAs 也被证明在预测 GDM 的发生及其长期心血管代谢并发症方面是有效的。迄今为止进行的研究表明，遗传和表观遗传技术有可能对临床护理产生影响，尽管还有很多工作要做。
