Genetics of Gestational Diabetes Mellitus

Abstract

About 2-5% of all pregnant women develop gestational diabetes mellitus (GDM) during their pregnancies and the prevalence has increased considerably during the last decade. GDM is a heterogeneous disorder that is defined as carbohydrate intolerance with onset or first recognition during pregnancy. It is manifested when pancreatic beta cells are no longer able to compensate for the increased insulin resistance during pregnancy, but the pathogenesis of the disease is still largely unknown. GDM is considered to result from interaction between genetic and environmental risk factors. Genetic predisposition to GDM has been suggested since GDM clusters in families. Also, women with mutations in MODY (Maturity onset diabetes of the young) genes often present with GDM. In addition, common variants in several candidate genes (e.g. potassium inwardly rectifying channel subfamily J, member 11 [KCNJ11], Glucokinase [GCK], Hepatocyte nuclear factor-1alpha [HNF1A] etc.) have been demonstrated to increase the risk of GDM. Old age, obesity and high fat diet represent some important non-genetic factors. There are several approaches to search for genes predisposing to a polygenic disease like GDM including linkage and association studies, expression profiling and animal models. A combination of several methods is usually necessary. Identification of the underlying genetic causes of GDM will eventually give a better view of the mechanisms that contribute to the pathophysiology of the disease. Furthermore, it may improve options to possibly prevent GDM and complications for the mother and her child. This review focuses on the genetics of GDM and possible implications in clinical practice.

A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus

“…Gestational diabetes mellitus is a heterogeneous disorder where genetic and environmental factors interact to cause the disease [1,2]. Studies have demonstrated that gestational diabetes mellitus shares some genetic and phenotypic features with other types of diabetes such as type 1, type 2 and MODY [1,2].…”

“…Studies have demonstrated that gestational diabetes mellitus shares some genetic and phenotypic features with other types of diabetes such as type 1, type 2 and MODY [1,2]. However, different risk alleles/genes might be operative in different types of diabetes and gestational diabetes mellitus due to the heterogeneous nature of these disorders.…”

“…Studies have consistently shown that women with a family history of diabetes have an increased risk of gestational diabetes mellitus [5,6]. In addition, we and others have demonstrated that gestational diabetes mellitus shares some genetic risk factors with type 2 diabetes [2]. For example, potassium inwardly rectifying channel subfamily J, member 11 (KCNJ11 E23K), glucokinase (GCK −30G>A) and transcription factor 1, hepatic; LF-B1, hepatic nuclear factor (HNF1), albumin proximal factor (TCF1, also known as hepatocyte nuclear factor 1-α [HNF1A I27L]) polymorphisms, all of which have been associated with type 2 diabetes [7][8][9], also increase the risk of gestational diabetes mellitus with a modest effect size [10,11].…”

“…Genetic and epidemiological studies suggest an association between gestational diabetes mellitus and type 2 diabetes [1,2]. The prevalence of gestational diabetes mellitus is increasing in parallel with the increased prevalence of type 2 diabetes [1,2].…”

“…The prevalence of gestational diabetes mellitus is increasing in parallel with the increased prevalence of type 2 diabetes [1,2]. The former is a common metabolic disorder of pregnancy, affecting at least 2% of Scandinavian women and 5 to 10% of Asian, Hispanic/Mexican American, and Arabian women [2]. Gestational diabetes mellitus occurs when pancreatic beta cells are unable to compensate for increased insulin resistance during pregnancy [3].…”