IDDM12 LOCUS ANALYSIS IN T1DM – IDENTIFICATION AND CHARACTERIZATION OF FUNCTIONAL POLYMORPHISMS

Several genes, besides HLA, contribute to type 1 diabetes. Their effect is relatively modest, but it is very important to detect them so that the single steps of the pathogenic process in which they intervene can be defined. Such dissection of the disease process will hopefully lead to prevention and even to therapy. More specifically, the genome region that we intend to study, the IDDM12 locus, includes several genes that participate in the regulation of the immune response. Since diabetes originates from an autoimmune reaction, it is likely that one or more of these genes influence the pathogenic process and a rather strong experimental evidence exists confirming this concept. We will study if in diabetic patients there are particular variations in the ICOS gene mapped in the IDDM12 region and we intend to confirm their association with the disease. Moreover, we will investigate the functional relevance of the CTLA4 variations already identified in the gene. In general, the significance and importance of genetic studies in T1DM lies in the perspective of dissecting the biologic pathways that contribute to autoimmune disease and to use that knowledge to slow or even reverse the destruction of self. This is even more relevant in the IDDM12 region which contains a number of genes that are known to be directly involved in the control of the immune response.