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What 'diabetogenes' may reveal about the risk, pathogenesis and genetics of type 2 diabetes
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PHILADELPHIA – There has been a tour de force of information about the genetics of diabetes during the last decade, C. Ronald Kahn, MD, said at the Therapeutic Insights from New Diabetes Gene Discoveries conference, held here.
Most recently, findings from wide single nucleotide polymorphism association studies have opened a new window for the geneticist in defining potential diabetogenes, as Kahn called them.
The nine loci that have been identified and associated with type 2 diabetes only explain a small proportion of familial clustering, according to Kahn, vice chairman and section chief of obesity a the Joslin Diabetes Center, Boston. The molecular mechanisms of the diabetogenes remain unknown.
“There is a progressive pathogenesis for insulin resistance, beta cell dysfunction and impaired glucose tolerance in type 2 diabetes,” he said.
Most of the genes are broadly expressed. For example, in the beta cell, the zinc transporter, SLC30, is the highest site of expression and in the fat cells, PPARG is the highest site of expression. Interestingly, according to Kahn, the brain is the highest level of expression in a number of type 2 diabetes genes, including TCF7L2 and FTO.
These risk alleles are common. About 85% of the U.S. population has five to nine of the risk allels and less than 1% has two or fewer alleles, he said. The average diabetes risk for the white population aged 21 and older is 7.5% to 8%, he said.
This knowledge may challenge the basic assumptions about the role of genetics in diabetes, according to Kahn. – by Katie Kalvaitis
For more information:
- Kahn RC. Genome-wide association studies: what they tell us and what they don’t. Therapeutic Insights from New Diabetes Gene Discoveries. March 18-19, 2008; Philadelphia.