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Insulin-Resistance Variant Identified

Posted: Wednesday, September 16, 2009

An international consortium of scientists has identified a new genetic variant associated with Type 2 diabetes, insulin resistance, and hyperinsulinemia , Dr. Johan Rung Cambridge, UK, and colleagues report.

Senior author Dr. Robert Sladek (McGill University, Montreal, QC) explained why this find is so significant, "Most of the diabetes genes identified until now have been associated with beta-cell function in the pancreas, and the question was always, 'Why aren't we finding the other half of the story?' "

The variant, or single nucleotide polymorphism (SNP), located adjacent to the insulin-receptor substrate 1 gene (IRS1), was discovered using genomewide association data from more than 14,000 French and Scandinavian individuals. And, in a novel twist, Sladek said they are "pretty sure the SNP is working through the gene," because further work showed that in human skeletal-muscle biopsies from people with the variant, there was about a 40% reduction in basal levels of the IRS1 protein and an equivalent reduction in this protein's activity, "which means that even if insulin is present, it won’t work."

However, Sladek cautions that although the SNP is adjacent to the IRS1 gene, it is in fact, "a long way away in genetic terms: 530 kb [kilobases] away, but despite this distance we can see some evidence of an effect." While there are no immediate clinical implications from this discovery, he says, "What we have is an SNP and a defined molecular event. Now we need to connect the dots in question, although there may be a lot of dots to connect."

Source: Diabetes In Control: Rung J, Cauchi S, Albrechtsen A, et al. Genetic variant near IRS1 is associated with Type 2 diabetes, insulin resistance and hyperinsulinemia. Nat Genet 2009; DOI:10.1038/ng.443. Abstract

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