Issue: January 2006
February 01, 2006
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Variant gene an intriguing find for diabetes research

If further research confirms it is important causative factor, it could prove a useful target for pharmacogenomic intervention.

Issue: January 2006
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Discovery of a variant gene that appears linked to a propensity for development of type 2 diabetes has been recognized as an important, yet early, step toward a useful clinical application.

Researchers at Decode Genetics in Reykjavik, Iceland, reported in Nature Genetics that the variant gene has been identified in Danish, American and Icelandic cohorts. Struan F. A. Grant and colleagues reported that the variant was “identified in a previously unknown candidate gene for type 2 diabetes, TCF7L2, within a previously reported linkage region on 10q.”

The data from the three populations “constitute strong evidence in support of the notion that variants of the TCF7L2 gene contribute to the risk of type 2 diabetes,” they wrote.

For heterozygous carriers of the at-risk alleles, estimated at 38% of the population, the relative risk of type 2 diabetes is 1.4; for homozygous carriers, an estimated 7% of the population, the risk is 2.41. That corresponds to a “population attributable risk” of 21%, Grant and colleagues wrote.

Lawrence Horwitz, MD, a cardiologist at the University of Colorado Hospital, said that a genetic propensity for this disease has long been suspected because of such factors as strong familial occurrence and high incidence in certain racial populations.

“However, convincing evidence implicating a specific genetic abnormality as a major cause of susceptibility to type 2 diabetes has been lacking,” he said.

Clinical implications

Samy I. McFarlane, MD, said that the finding “could have a significant impact in the future on strategies for prevention and management of the disease.

“For example, patients with the gene, especially the patients who are homozygous carriers, could be identified early through screening and have targeted interventions, such as diet and exercise, and if necessary, medications.”

McFarlane is chief of the division of endocrinology, diabetes and hypertension at State University of New York and associate medical editor of Endocrine Today.

Horwitz said that if the abnormality proves to be an important causative factor after additional research, it might become a useful target for pharmacogenomic intervention. “However, development of such a treatment is likely to take considerable time before it can be employed clinically.”

Future research

The statistical strength of the association of the genetic allele with type 2 diabetes was clear in the Decode Genetics trial, but the absolute differences from the control groups were small, Horwitz said. “Since overt evidence of type 2 diabetes appears to depend on environmental factors, this is not unexpected,” he said.

Some members of the control groups with the allele may have had susceptibility to the disease, Horwitz said, but in the absence of factors such as obesity, this may not have been detectable.

Because the size of the population groups included in the study was small, future research should include larger groups to confirm the importance of the genetic abnormality in other groups, Horwitz said.

“It is entirely possible, if not likely, that other genetic abnormalities are also of importance in the genesis of type 2 diabetes,” he said. – by Kathy Holliman

For more information:
  • Grant SFA, Thorleifsson G, Reynisdottir I, et al. Variant of transcription factor 7-like (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. Published online Jan. 15, 2006.