A study by the UPV/EHU has concluded that non-coding genes, and therefore not very studied to date, may be important in the pathogenesis of diseases. By studying the effect that one of these genes has on insulin-producing cells, they have concluded that a viral infection can activate certain processes that could lead the cell to its destruction.
Type I diabetes, or insulin dependent, appears in youth or childhood. About 10-15% of types of diabetes are in that category. It is considered an autoimmune disorder: the destruction of the beta cells itself occurs, and they stop producing insulin. “It is a very complex autoimmune, inflammatory and polygenic disease. People who develop it have a particular genetics, but we know that a number of other factors can also play a role in activating the disease. There are numerous investigations that have discovered viral traces in the pancreatic beta cells of people who have developed diabetes, something that is not found in non-diabetic people. Starting from that point, we have found an interaction between viral infections and a non-coding gene that can increase the risk of developing the disease ”, explains the professor of Biochemistry and Molecular Biology at UPV / EHU Izortze Santin Gomez.
Dr. Santin is dedicated to the functional research of genes related to type I diabetes; specifically, it studies "the function that these genes play in beta cells (the cells that produce insulin), to know the effect they have on the pathogenesis or development of the disease." He has investigated the influence of a polymorphism that appears in the Lnc13 gene, a non-coding gene related to type I diabetes, in collaboration with the researcher Ikerbasque and member of the Department of Genetics, Physical Anthropology and Animal Physiology of the UPV / EHU Ainara Castellanos -Rubio. "Until now, importance has been given above all to the candidate genes that encode proteins, and not much attention has been paid to other polymorphisms that are found in non-coding areas of proteins, but we think that these may have a great influence on the development of certain diseases ”, says Santin. Thus, the research group has determined what role the non-coding gene Lnc13 plays in pancreatic beta cells that have suffered a viral infection, and through what molecular mechanisms it does. The prestigious scientific journal PNAS has published the study.
A new variable in the equation that determines the onset of diabetes
In their research, they have reached a series of important conclusions: “On the one hand, when a viral infection occurs in beta cells, the expression of the Lnc13 gene increases. On the other hand, it is Lnc13 that regulates inflammation of beta cells: the metabolic pathway that is activated when Lnc13 is increased can cause cells of the immune system to migrate to beta cells, and this effect is totally related to the inflammatory process that occurs in diabetes (insulitis). We have seen that in people suffering from a viral infection, a variant (allele) of Lnc13, which increases the risk of developing diabetes, can cause a process of excessive inflammation, which can induce the destruction of beta cells. ”
Santin points out the three general and very important conclusions that they have reached with the results obtained in his research: “Polymorphisms in the non-coding area of the genome, which until now have not been taken into account, can have important functions and may be related to the appearance of certain diseases. So it is possible that from now on we have to start taking them into account. ” On the other hand, in relation to type I diabetes, "we can say that the search for a certain variant (allele) in the study of the genotype of the Lnc13 gene or the search for traces of viral infections can have a predictive value," he explains. And finally, all of the above opens the doors to the implementation of a gene therapy: "You can activate the modulation of the pathogenic inflammatory pathway that we have found in our research, playing with the expression of genes from the non-coding area."
"It is clear that diabetes is a complex and polygenic disease," concludes Santin. therefore, there is no doubt that the Lnc13 gene is not the only factor that explains the onset of diabetes, but it is time to enter the study of the non-coding area of the genome, as well as to include Lnc13 in the equation that explains the genetics of the disease. It is still too early to use it in the treatment of diabetes, but all this would make it possible to see if, by playing with the expression of Lnc13 at the beta cell level, we could stop or not the pathogenic effect caused by viral infections ”.
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