Influence of type 1 diabetes genes on disease progression: similarities and differences between countries

Type 1 diabetes (T1D) is an autoimmune disease causing the destruction of pancreatic beta cells. The onset of clinical T1D is preceded by a time period called pre-diabetes, the duration of which varies widely. However, not all subjects developing beta-cell autoimmunity progress to clinical T1D. The inherited risk for T1D is determined by the human leukocyte antigen (HLA) class II genes, HLA class I genes, and several loci outside the HLA area. Although the role of the genetic risk variants in disease pathogenesis is not completely understood, some of the variants affecting disease risk are thought to influence the initiation of beta-cell autoimmunity whereas others seem to play a role during the later stages of the autoimmune process. In this review we describe the current knowledge on the genetic factors mediating the fate of already-established beta-cell autoimmunity and the rate of beta-cell destruction.