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Searching for type 2 diabetes genes: prospects in pharmacotherapy

The Pharmacogenomics Journal volume 2, pages 25–29 (2002)Cite this article

Type 2 diabetes is a complex, heterogeneous group of metabolic disorders that has reached epidemic proportions, affecting over 5% of the population in western countries. The pathophysiology of type 2 diabetes includes two apparently distinct defects, ie impairments in insulin action at the level of skeletal muscle, fat and liver, and a failure in insulin secretory capacity of pancreatic β-cells. There is strong evidence that genetic factors play an important role in both of these components given the familial nature, the high concordance rate between monozygotic twins, and the high prevalence in certain ethnic groups.1 However, identifying genes that confer susceptibility to type 2 diabetes has proven problematic. The search for diabetes-predisposing genes has mainly relied on two complementary approaches: (1) the candidate genes analysis; and (2) the positional cloning using genome-wide linkage analysis. A number of genes have been screened as putative candidates and several polymorphisms in coding and promoter regions have been tested in case-control association studies. So far, only one gene predisposing to the common form of type 2 diabetes has been identified by positional cloning,1 while this approach was successfully employed to identify genes responsible for rare monogenic forms of diabetes such as maturity-onset diabetes of the young (MODY).2,3,4,5,6,7 Here, I will review results of studies of ‘functional’ and ‘positional’ candidate genes predisposing to type 2 diabetes, focusing on those that may influence the variability in patients’ response to antidiabetic drugs or may be amenable to pharmacological intervention.

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  1. Department of Experimental and Clinical Medicine, University of Catanzaro–‘Magna Græcia’, Catanzaro, Italy

    G Sesti

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Sesti, G. Searching for type 2 diabetes genes: prospects in pharmacotherapy. Pharmacogenomics J 2, 25–29 (2002). https://doi.org/10.1038/sj.tpj.6500078

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