Authors: Shaat, Nael; Groop, Leif

Source: Current Medicinal Chemistry, Volume 14, Number 5, February 2007 , pp. 569-583(15)

Publisher: Bentham Science Publishers

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.

Keywords: Association; GDM; Genetics; Gestational diabetes mellitus; MODY; Polymorphism; Type 1 diabetes; Type 2 diabetes

Document Type: Research article

DOI: http://dx.doi.org/10.2174/092986707780059643

Affiliations: 1: Department of Clinical Sciences/Diabetes & Endocrinology, Malmo University Hospital, Lund University, Malmo, Sweden.

Publication date: 2007-02-01

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• Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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