Ortega-Contreras B, Armella A, Appel J, Mennickent D, Araya J, González M, Castro E, Obregón A M, Lamperti L, Gutiérrez J, Guzmán-Gutiérrez E
Pregnancy Diseases Laboratory, Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, Universidad de Concepción, Concepción, Chile.
Department of Instrumental Analysis, Faculty of Pharmacy, Universidad de Concepción, Concepción, Chile.
Front Physiol. 2022 Apr 4;13:769924. doi: 10.3389/fphys.2022.769924. eCollection 2022.
Gestational Diabetes Mellitus (GDM) is a highly prevalent maternal pathology characterized by maternal glucose intolerance during pregnancy that is, associated with severe complications for both mother and offspring. Several risk factors have been related to GDM; one of the most important among them is genetic predisposition. Numerous single nucleotide polymorphisms (SNPs) in genes that act at different levels on various tissues, could cause changes in the expression levels and activity of proteins, which result in glucose and insulin metabolism dysfunction. In this review, we describe various SNPs; which according to literature, increase the risk of developing GDM. These SNPs include: (1) those associated with transcription factors that regulate insulin production and excretion, such as rs7903146 () and rs5015480 (); (2) others that cause a decrease in protective hormones against insulin resistance such as rs2241766 () and rs6257 (); (3) SNPs that cause modifications in membrane proteins, generating dysfunction in insulin signaling or cell transport in the case of rs5443 () and rs2237892 (); (4) those associated with enzymes such as rs225014 () and rs9939609 () which cause an impaired metabolism, resulting in an insulin resistance state; and (5) other polymorphisms, those are associated with growth factors such as rs2146323 () and rs755622 () which could cause changes in the expression levels of these proteins, producing endothelial dysfunction and an increase of pro-inflammatory cytokines, characteristic on GDM. While the pathophysiological mechanism is unclear, this review describes various potential effects of these polymorphisms on the predisposition to develop GDM.
妊娠期糖尿病(GDM)是一种高度常见的母体疾病,其特征是孕期母体葡萄糖不耐受,且与母亲和后代的严重并发症相关。多种风险因素与GDM有关;其中最重要的因素之一是遗传易感性。在不同组织中发挥不同作用的基因中的众多单核苷酸多态性(SNP),可能导致蛋白质表达水平和活性发生变化,进而导致葡萄糖和胰岛素代谢功能障碍。在本综述中,我们描述了各种SNP;根据文献,这些SNP会增加患GDM的风险。这些SNP包括:(1)与调节胰岛素产生和分泌的转录因子相关的SNP,如rs7903146()和rs5015480();(2)其他导致抗胰岛素抵抗保护激素减少的SNP,如rs2241766()和rs6257();(3)导致膜蛋白修饰的SNP,在rs5443()和rs2237892()的情况下会导致胰岛素信号传导或细胞转运功能障碍;(4)与酶相关的SNP,如rs225014()和rs9939609(),这些酶会导致代谢受损,从而导致胰岛素抵抗状态;(5)其他多态性,与生长因子相关,如rs2146323()和rs755622(),这些多态性可能导致这些蛋白质表达水平发生变化,产生内皮功能障碍并增加促炎细胞因子,这是GDM的特征。虽然病理生理机制尚不清楚,但本综述描述了这些多态性对发生GDM易感性的各种潜在影响。