Genetic and functional evidence supporting SUMO4 as a type 1 diabetes susceptibility gene

Ann N Y Acad Sci. 2006 Oct;1079:257-67. doi: 10.1196/annals.1375.039.


Genomewide linkage analyses since the early 1990s suggested over 20 genomic intervals that may contain susceptibility genes for type 1 diabetes. However, the identification of the specific genes in these intervals presents a formidable challenge due to a number of difficulties associated with genetic mapping and cloning of genes implicated in complex diseases. One of the difficulties is due to the presence of many weak and different susceptibility genes in different patients and populations, a phenomenon known as genetic heterogeneity. In 2004, we reported the cloning of a novel small ubiquitin-like modifier (SUMO) gene, SUMO4, in the IDDM5 interval on chromosome 6q25, and presented strong genetic and functional evidence suggesting that SUMO4 is a susceptibility gene for type 1 diabetes mellitus (T1DM). In this article, we will summarize genetic association data suggesting that SUMO4 is consistently associated with T1DM in the Asian populations while the association is more heterogeneous in the Caucasian populations. We will also discuss the possible molecular pathways through which sumoylation may regulate T1DM and autoimmunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autoimmune Diseases / genetics
  • Chromosomes, Human, Pair 6
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / metabolism*
  • European Continental Ancestry Group / genetics
  • Forecasting
  • Genetic Heterogeneity
  • Genetic Linkage
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Humans
  • Microsatellite Repeats
  • Mutation
  • Physical Chromosome Mapping
  • Reproducibility of Results
  • Small Ubiquitin-Related Modifier Proteins / genetics*


  • Genetic Markers
  • Small Ubiquitin-Related Modifier Proteins