New diabetes genes identified in the pancreas of European and American patients

A European research team, led by Professor Philippe Froguel from the Integrative Genomics and Metabolic Disease Modeling laboratory (Institut Pasteur de Lille / University of Lille / CNRS), has just discovered new genes that contribute to the risk of type 2 diabetes and to the secretion of insulin.

Published in Molecular Metabolism, this study also associates Imperial College London, Paul Langerhans Institute in Dresden, the University of Pisa and the pharmaceutical companies Sanofi and Lilly, as part of a public-private partnership co-funded by the European Union via the IMI Horizon 2020 program. This discovery paves the way for a new generation of diabetes treatments.

To date, more than 200 genes have been identified, but researchers have encountered the complexity of defining their role and contribution to diabetes, making the development of new drugs difficult. Faced with this problem, the European research team has developed a new approach called eQTL which consists in studying the impact of DNA mutations (or variants) increasing the risk of diabetes on the activity of genes located near these genetic variants. The challenge for this type of study is to gain access to the most important organ of diabetes, the pancreas, and more specifically the pancreatic islets of cells that secrete insulin. To do this, it is essential to study a large number of human samples and therefore to work in an international framework. The originality of this work is therefore the number of patients who were studied (200) but also the typology of the patients: for the first time, the researchers were able to carry out this research from living diabetic patients operated on for pancreatic disease and not from deceased organ donors.
Using this unique resource in the world and this new scientific method, European researchers have obtained a catalog of more than 1000 regions of the eQTL-type genome. One of the findings of the study was that, in a large number of cases, the pancreatic gene in question was not located in close proximity to the genetic variant, which opens up new hypotheses on the genetic and physiological origin of diabetes. . Indeed, the DNA, being folded in the nucleus, the eQTL approach makes it possible to have a 3-dimensional map of the genes of diabetes. This work offers a unique database to public and private researchers around the world towards new therapies and more personalized medicine for diabetes.

This work is the result of an international collaboration involving public research laboratories and teams from the European pharmaceutical industry.

Khamis A. et al. “Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated with type 2 diabetes”, Mol. Metab. 2019

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