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Genetics of Gestational Diabetes Mellitus and Type 2 Diabetes

¹ Department of Preventive Medicine, Division of Biostatistics, Keck School of Medicine of USC, Los Angeles, California
² Department of Physiology and Biophysics, Keck School of Medicine of USC, Los Angeles, California
³ Institute for Genetic Medicine, Keck School of Medicine of USC, Los Angeles, California
⁴ Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California
⁵ Department of Medicine, Division of Diabetes and Endocrinology, Keck School of Medicine of USC, Los Angeles, California

Address correspondence and reprint requests to Richard M. Watanabe, PhD, Department of Preventive Medicine, Keck School of Medicine of USC, 1540 Alcazar St., CHP-220, Los Angeles, CA 90089-9011. E-mail: rwatanab@usc.edu

Abbreviations: 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 first 300 words of the full text of this article appear below.

	INTRODUCTION

 
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.

	GENETICS OF DIABETES

 
Type 1 diabetes and rare/monogenic forms of diabetes
The HLA region on chromosome 6 was identified very early on as a major susceptibility gene for type 1 diabetes (2–4), with haplotypes within the HLA region accounting for as much as 50% of cases of type 1 diabetes in Caucasians (4). While the contribution of HLA to genetic susceptibility to type 1 diabetes was readily identified, numerous genome scans have also identified at least 16 additional loci across the genome that may harbor susceptibility genes . . . [Full Text of this Article]

Type 2 diabetes
Chromosome 20
The fall and rise of HNF4A.

	GENETICS OF GDM

 
Familial clustering
Candidate genes
HNF4A in GDM.

	THE FUTURE—

 

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