Two interacting genes, both unlikely suspects as a cause of adult-onset diabetes, have now been convicted. Mutations of either gene trigger an early-onset form of this extremely prevalent disease, report research teams based at the University of Chicagos Howard Hughes Medical Institute, the Rockefeller University (New York), the University of Michigan, the Wellcome Trust Centre for Human Genetics in Oxford, England, and the Institute Pasteur de Lille, France, together with other investigators from Denmark, Japan and the United Kingdom, in back-to-back papers in the December 5 issue of Nature.
Both genes evaded scrutiny for years because neither was thought to be involved in the control of blood glucose levels.
But two overlapping research teams, each led by Graeme Bell, Ph.D., Louis Block Professor of Biochemistry & Molecular Biology and of Medicine in the University of Chicagos Howard Hughes Medical Institute, traced the disorder to mutations of two similar genes one on chromosome 12 and one on chromosome 20 that regulate the activity of other genes.
"Both of these are known genes but neither one was considered likely to play a role in diabetes," said Bell.
Both genes turned out to be "transcription factors," proteins that control how and when other genes are turned on or off. Both were known to be active in regulating gene expression in the liver, kidney and intestine.
"This surprising finding means we have to quit thinking of diabetes purely as a defect in glucose metabolism and starting thinking of it as possibly a defect in gene expression," said Bell. "That makes diabetes a more complicated disorder, but it also opens up new ways of treating it.
"The discovery of these genes means that we have to place more emphasis on treating diabetes in families rather than in individual patients," added Bell. "We need to screen the brothers and sister
Contact: John Easton
University of Chicago Medical Center