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Elucidation of the genome for diabetics with DNA chips

to explore genetic predisposition to DT2 in its entirety. In 2006, a revolutionary genetic analysis technique was developed in the United States. This method is based on the use of DNA chips, with a surface of only a few square centimetres, carrying almost half a million DNA mutations. Each of these chips can be used to dissect the entire genome of an individual.

Initially, DNA from non-obese patients with type 2 diabetes and a family history of the disease was compared with DNA from 669 non-diabetic subjects from the DESIR study, a prospective study run by INSERM and directed by Beverly Balkau. The key results of this first screening were then confirmed in more than 5500 French diabetic patients treated at Corbeil-Essonnes Hospital (Guillaume Charpentier) and Poitiers University Hospital (Samy Hadjadj) and in additional control subjects. These results demonstrate very strong associations between DT2 and at least four genes encoding proteins playing major roles in the development of the pancreas and of insulin-producing cells: TCF7L2, HHEX, EXT2 and SLC30A8.

  • TCF7L2 and HHEX encode transcription factors (molecules regulating the activity of other genes) controlling the Wnt signalling pathway essential for cell survival. Studies in animals have shown that the absence of these genes impairs pancreatic function.
  • EXT2 encodes an enzyme involved in the foetal development of several organs, including the pancreas. This enzyme also regulates Wnt signalling.
  • Finally, the SLC30A8 gene encodes the ZnT8 protein, which is involved in zinc transport. This protein is involved in insulin binding in the pancreas. According to the work of the French team directed by P. Froguel and Mellitech, a biotech company from Grenoble, ZnT8 is the only molecule apart from insulin produced exclusively in the insulin-secreting beta cells of the pancreas. Zinc is a trace element present in very small amounts in the body, but essential for su
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