Sumoylation Modulates the Susceptibility to Type 1 Diabetes

Susceptibility to type 1 diabetes (T1D) is determined by interactions of multiple genes with environmental triggers. Thus far, more than 50 T1D susceptibility regions have been suggested from genetic studies by employing either genome-wide or candidate gene approaches. Because the lack of a linear correlation between the presence of risk genes and the onset of disease, the exact susceptible genes encoded in these regions remain largely elusive. In 2004, we first reported the cloning of a novel small ubiquitin-like modifier (SUMO) gene, SUMO4, in the IDDM5 region on chromosome 6q25, and presented strong genetic and functional evidence suggesting that SUMO4 could be a novel T1D susceptibility gene. Follow up studies have consistently confirmed this association in multiple Asian populations despite controversial observations in Caucasians, which could be caused by genetic heterogeneity. In this chapter, we will summarize and validate genetic data for SUMO4 association studies in type 1 diabetes. The functional properties and possible molecular mechanisms by which altered sumoylation function modulates the development of type 1 diabetes will be also discussed based on published data.