Genetics of Gestational Diabetes Mellitus and Type 2 Diabetes

• GDM, gestational diabetes mellitus
• FUSION, Finland-U.S. Investigation of Non-Insulin-Dependent Diabetes Mellitus
• MODY, maturity-onset diabetes of the young
• SNP, single-nucleotide polymorphism

The successful application of positional cloning, the process of disease susceptibility gene identification using gene mapping techniques, to identify the gene underlying cystic fibrosis (1) opened the era of gene hunting. The subsequent identification of susceptibility genes underlying numerous monogenic disorders led to the possibility that susceptibility genes for complex diseases could also be identified using the positional cloning approach. This, coupled with advances in both genotyping technology and the identification of large numbers of microsatellite markers across the genome, led to numerous genome-wide scans to identify susceptibility genes for various forms of diabetes. However, despite the genetic screening of genes known to be involved in the biology of diabetes (candidate genes) and positional cloning approaches, to date, few susceptibility genes for diabetes have been identified. Even less is known about the genetic basis for gestational diabetes mellitus (GDM). The inability to readily identify susceptibility genes for diabetes can be attributed to a variety of issues, including insufficient statistical power, etiologic heterogeneity, and the confounding effect of interactions with environmental factors. These same problems will likely apply to GDM, which appears to represent early stages of many forms of diabetes outside of pregnancy. Here, we briefly review the current state of knowledge regarding the genetics of diabetes and discuss specific issues regarding the genetics of GDM.