Genetics of Type 1 diabetes mellitus

Type 1 diabetes or insulin-dependent diabetes mellitus (IDDM) is the archet ypal example of a T cell-mediated autoimmune disease characterised by selec tive destruction of a single cell type: the insulin-producing beta-cens of the pancreatic islets of Langerhans. The pathogenic equation for IDDM prese nts a complex interrelation of genetic and environmental factors, most of w hich have yea to be identified. Based on the observed familial aggregation of IDDM, it is certain that there is a decided heritable genetic susceptibi lity for developing autoimmune diabetes. The well-known association of IDDM ,with certain human histocompatibility leukocyte antigen (HLA) alleles of t he major histocompatibility complex (MHC) was a major step toward understan ding the role of inheritance in IDDM, Landmark molecular biological investi gations of diabetes HLA susceptibility genes provided great potential for i nsights into the molecular basis for the autoimmune nature of the disease, beginning a story that continues to unfold. Although the association of cer tain HLA alleles with IDDM is very strong, this genetic locus is estimated to account for less than 50 % of genetic contributions to disease susceptib ility. The search for non-HLA susceptibility genes has received great atten tion in recent years. Albeit genome wide searches are wrought with controve rsy, such studies have suggested the association of numerous non-MHC loci w ith Type 1 diabetes that sill require careful follow-up investigation, Cell biological and genetic functional analyses will provide clues that are ind ispensable for further progress. The necessary studies include research on immunological abnormalities that are present many years before the clinical onset of Type 1 diabetes. (C) 1999, Editrice Kurtis.