New insights into the possible cause of type 2 diabetes
Researchers from the KG Jebsen Center for Diabetes Research, in collaboration with researchers from the Broad Institute of Harvard and MIT, Massachusetts General Hospital (Boston/Cambridge, USA) and researchers in Mexico, found a new risk variant for type 2 diabetes in patients from a Latino population. The project is part of the "SIGMA Type 2 Diabetes Consortium"; a project funded by the world's richest man Carlos Slim.
This study provides new insights into the possible cause of type 2 diabetes in specific populations, and may have implications for improved diagnostics and treatment in these populations.
Researchers from the KG Jebsen Center for Diabetes Research, University of Bergen and Haukeland University Hospital, have been responsible for the protein analyses investigating the effect of this rare gene variant on protein function, and played also an important role in the writing of the article.
The results are published in June in the prestigious Journal of the American Medical Association (JAMA), which is among the world's most widely read general medical journals.
Prevalence of type 2 diabetes is generally high in the world. Among Latino populations in USA and Mexico the prevalence is among the highest with twice as many cases seen in Mexican-Americans compared to whites. To search for the cause for this high prevalence, whole-exome sequencing of a large Latino population and controls was performed. A rare variant in the HNF1A gene was found more frequently in diabetic versus healthy individuals, and the findings were also confirmed in an even larger multi-ethnic material of type 2 diabetes patients. Interestingly, the variant is located in a gene that is linked to monogenic diabetes (MODY3) and encodes the transcription factor HNF-1A. Researchers in Bergen have studied HNF-1A function in cell models and demonstrated that the gene variant affects HNF1A activity (reduced) compared to the normal protein. In addition, the mutant protein was expressed at a lower level and showed an abnoral distribution in the cell compared to the normal HNF-1A protein.
The protein assays were performed by PhD student Laeya Najmi in Bergen. Researcher Lise Bjørkhaug Gundersen and post doc Ingvild Aukrust lead the analyses. Head of the KG Jebsen Center, Pål Rasmus Njølstad, coordinated the studies between Bergen and USA.
Read the JAMA article here.