deCODE Discovers Major Genetic Risk Factor for Type 2 Diabetes

"This is a milestone in human genetics. A common gene variant conferring elevated risk of T2D has been earnestly sought by the genetics community for many years. We have found such a variant, which we estimate accounts for about 20% of T2D cases. This discovery sheds new light on the biological causes of the disease. Importantly, virtually all of this risk can be captured by looking at a single-letter change in DNA - ideal for the development of a genetic test for assessing individual risk and developing more personalized and effective prevention strategies. This is also an exciting starting point for the discovery of new drugs, and we are actively pursuing the development of both diagnostic and therapeutic products to better prevent and treat T2D," said Kari Stefansson, CEO of deCODE and senior author on the study.

The variant is located in a gene encoding a protein called transcription factor 7-like 2 (TCF7L2). deCODE isolated the gene by following up on the results of a population-based, genome-wide linkage scan in Iceland that identified a promising region on chromosome 10. The deCODE team genotyped 228 microsatellite markers - polymorphic signposts along the genome - in this region in a total of more than 2000 patients and controls. Analysis of the frequency of different alleles, or versions, of these markers pinpointed a version of one marker within the gene encoding TCF7L2 that is approximately 1.5 times more common in patients than in controls. This corresponds to a 50% increase in risk of T2D per copy carried (there are two copies of each chromosome in every cell).

This finding was replicated in Danish and U.S. cohorts, where the at-risk version of the marker was found to confer an increased risk of 41% and 85%, respectively, per copy carried. For all of the cohorts combined, the at-risk allele confers an increase in risk of approximately 45% for those carrying one copy, and a 141% increase in risk for individuals carrying two copies. Utilizing data from the HapMap project, a SNP was found that correlates nearly perfectly with the at-risk microsatellite.

Diabetes: A major public health problem
Diabetes affects nearly 200 million people worldwide and an estimated 21 million in the United States - 7% of the population. The vast majority of diabetes patients have type 2 diabetes, a condition where the body does not produce enough insulin and/or the cells in the body do not properly use insulin. In the United States, the direct medical cost associated with diabetes is nearly $100 billion per year. The incidence of type 2 diabetes is increasing rapidly in the industrialized world, in part due to the increase in obesity, one of the major risk factors for developing the disease.

About deCODE
deCODE genetics (Nasdaq:DCGN) is a biopharmaceutical company applying its discoveries in human genetics to the development of drugs for common diseases. deCODE is a global leader in gene discovery " our population approach and resources have enabled us to isolate key genes contributing to major public health challenges from cardiovascular disease to cancer, genes that are providing us with drug targets rooted in the basic biology of disease. deCODE is also leveraging its expertise in human genetics and integrated drug discovery and development capabilities to offer innovative products and services in DNA-based diagnostics, bioinformatics, genotyping, structural biology, drug discovery and clinical development. deCODE is delivering on the promise of the new genetics.SM Visit us on the web at www.decode.com.

(C) 2006 - deCODE genetics

Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes
Struan F A Grant, Gudmar Thorleifsson, Inga Reynisdottir, Rafn Benediktsson, Andrei Manolescu, Jesus Sainz, Agnar Helgason, Hreinn Stefansson, Valur Emilsson, Anna Helgadottir, Unnur Styrkarsdottir, Kristinn P Magnusson, G Bragi Walters, Ebba Palsdottir, Thorbjorg Jonsdottir, Thorunn Gudmundsdottir, Arnaldur Gylfason, Jona Saemundsdottir, Robert L Wilensky, Muredach P Reilly, Daniel J Rader, Yu Bagger, Claus Christiansen, Vilmundur Gudnason, Gunnar Sigurdsson, Unnur Thorsteinsdottir, Jeffrey R Gulcher, Augustine Kong & Kari Stefansson
Nature Genetics Published online: 15 January 2006 | doi:10.1038/ng1732

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