title: Sumoylation Modulates the Susceptibility to Type 1 Diabetes.
abstract: 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.
authors.affiliation: The Center for Biomedical Research, Key Laboratory of Organ Transplantation, Ministry of Education, Key Laboratory of Organ Transplantation, Ministry of Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The Center for Biomedical Research, Key Laboratory of Organ Transplantation, Ministry of Education, Key Laboratory of Organ Transplantation, Ministry of Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China.
authors.forename: Zhishui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Second Xiangya Hospital, and Diabetes Center, and Institute of Metabolism and Endocrinology, and Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Central South University, Changsha, 410011, China.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: The Center for Biomedical Research, Key Laboratory of Organ Transplantation, Ministry of Education, Key Laboratory of Organ Transplantation, Ministry of Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China. yangping@tjh.tjmu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: The Center for Biomedical Research, Key Laboratory of Organ Transplantation, Ministry of Education, Key Laboratory of Organ Transplantation, Ministry of Health, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China. wangcy@tjh.tjmu.edu.cn.
authors.forename: Cong-Yi
authors.initials: CY
authors.lastname: Wang
mesh_terms: D000818:Animals; D015551:Autoimmunity; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics* / Q000378:metabolism; D058207:Sumoylation; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: C489647:SUMO4 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D044767:Ubiquitin-Protein Ligases
keywords: Autoimmunity; Beta-cell; SUMO; Sumoylation; Type 1 diabetes