Current Opinion in Clinical Nutrition and Metabolic Care. 11(4):371–377, JULY 2008
DOI: 10.1097/MCO.0b013e32830349a1
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PMID: 18541994
Issn Print: 1363-1950
Publication Date: July 2008
New gene variants alter type 2 diabetes risk predominantly through reduced beta-cell function
John Perry;Timothy Frayling;
+ Author Information
Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
Abstract
Over the past 18 months, the number of gene loci robustly associated with type 2 diabetes has risen from three to 18. In this study, we focus on explaining the genome-wide approach that has led to most of these discoveries and discuss some of the early insights the new gene loci have provided into the aetiology of type 2 diabetes.Recent genome-wide association studies have provided an important resource for furthering our understanding of type 2 diabetes disease mechanisms. Genes previously unsuspected of playing a role in diabetes are now implicated in the disease process. These include genes in cell cycling control (CDKN2A/2B, CDKAL1), transcription factors (TCF7L2, HHEX), and ion channels (SLC30A8). These variants are all associated with insulin-secretory defects in the general population and show little if any relationship to insulin resistance. Two common variants (near or in FTO and MC4R) alter diabetes risk through a primary effect on obesity.Recent genome-wide association studies show that there are now 18 gene loci associated with the risk of type 2 diabetes. Most of these T2D gene loci affect insulin secretion.
