Gestational Diabetes Mellitus: The Genetic Susceptibility Behind the Disease

Abstract

Gestational diabetes mellitus (GDM), a type of pregnancy-specific glucose intolerance or hyperglycemia, is one of the most common metabolic disorders in pregnant women with 16.9% of the global prevalence of gestational hyperglycemia. Not only are women with GDM likely to develop T2DM, but their children are also at risk for birth complications or metabolic disease in adulthood. Therefore, identifying the potential risk factors for GDM is very important in the prevention and treatment of GDM. Previous studies have shown that genetic predisposition is an essential component in the occurrence of GDM. In this narrative review, we describe the role of polymorphisms in different functional genes associated with increased risk for GDM, and available evidence on genetic factors in the risk of GDM is summarized and discussed.

Genomics and Epigenomics of Gestational Diabetes Mellitus: Understanding the Molecular Pathways of the Disease Pathogenesis

“…Considering all of these observations, it is not surprising that both disorders may have a similar genetic basis. Therefore, T2DM susceptibility genes, as well as those that are involved in β-cell function, insulin response, and glucose regulation, have been identified as potential candidates for GDM [ 27 , 28 ]. Yahaya et al suggested that 83 candidate genes exist for GDM in a recent comprehensive review.…”

“…Transcription factor 7 like 2 (TCF7L2) is located on chromosome 10q25 [ 28 ]. It is highly expressed in adipose tissue, the pancreas, and several other tissues [ 53 ].…”

“…TCF7L2 is the strongest association with T2DM yet, and plays a role in glucose homeostasis [ 54 ]. TCF7L2 also regulates adipokines, signaling hormones secreted by adipocytes such as leptin and adiponectin [ 28 , 55 ]. Those hormones are involved in appetite regulation and energy expenditure [ 28 ].…”

“…TCF7L2 also regulates adipokines, signaling hormones secreted by adipocytes such as leptin and adiponectin [ 28 , 55 ]. Those hormones are involved in appetite regulation and energy expenditure [ 28 ]. Usually, leptin is elevated in GDM cases and is thought to contribute to macrosomia, while adiponectin is lower and associated with insulin resistance [ 1 ].…”

“…Several genetic mutations and disorders can disrupt the insulin secretion process, resulting in early termination of insulin production and the shortage of insulin seen in patients with T2DM and GDM [ 44 ]. Potassium voltage-gated channel subfamily Q member 1 ( KCNQ1 ) is a gene on chromosome 11p15 that is expressed in the kidney, brain, heart, and pancreatic islets [ 28 , 45 ]. It contributes to cell polarization and regulation of insulin secretion [ 44 , 65 ].…”