title: Evidence for the role of small ubiquitin-like modifier 4 as a general autoimmunity locus in the Japanese population.
abstract: BACKGROUND
  Recently, an association of a single nucleotide polymorphism, 163A>G encoding M55V, in the gene SUMO4, which has been shown to be a negative feedback regulator for nuclear factor kappaB, has been reported in type 1 diabetes.
  
  
  OBJECTIVE
  To establish whether SUMO4 locus contributes to the genetic susceptibility to other autoimmune disorders, a case-control analysis was carried out using genomic DNA from type 1 diabetes, autoimmune thyroid disease (AITD), rheumatoid arthritis (RA), and primary Sjögren's syndrome.
  
  
  METHODS
  A total of 1480 samples, including 929 cases (411 patients with type 1 diabetes, 292 AITD, 172 RA, and 54 primary Sjögren's syndrome) and 551 healthy control subjects of Japanese origin participated in the study.
  
  
  METHODS
  The 163A>G (rs237025, M55V) polymorphism of SUMO4 was genotyped.
  
  
  RESULTS
  SUMO4 M55V variant was associated not only with type 1 diabetes [odds ratio (OR), 1.42; 95% confidence interval (CI), 1.09-1.84; P = 0.0072], but also with increased risk of other autoimmune diseases, AITD (OR, 1.52; 95% CI, 1.14-2.03; P = 0.0041) and RA without amyloidosis (OR, 1.53; 95% CI, 1.65-2.24; P = 0.027), but not primary Sjögren's syndrome. Furthermore, the association of SUMO4 M55V variant was stronger in type 1 diabetic patients complicated with AITD (OR, 1.62; 95% CI, 1.06-2.47; P = 0.023) and in patients who have neither type 1 diabetes-susceptible class II HLA, DRB1*0405 nor DRB1*0901 (OR, 2.28; 95% CI, 1.34-3.87; P = 0.0018).
  
  
  CONCLUSIONS
  These results indicate that the SUMO4 is a more common autoimmune disease gene and a supplementary risk factor to type 1 diabetes in conjunction with class II HLA.
authors.affiliation: Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital of Medicine and Dentistry, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Tsurumaru
authors.forename: Eiji
authors.initials: E
authors.lastname: Kawasaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ida
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Migita
authors.forename: Akie
authors.initials: A
authors.lastname: Moriuchi
authors.forename: Keiko
authors.initials: K
authors.lastname: Fukushima
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fukushima
authors.forename: Norio
authors.initials: N
authors.lastname: Abiru
authors.forename: Hironori
authors.initials: H
authors.lastname: Yamasaki
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Noso
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegami
authors.forename: Takuya
authors.initials: T
authors.lastname: Awata
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
mesh_terms: D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics*; D013959:Thyroid Diseases / Q000235:genetics / Q000276:immunology
chemical_list: C489647:SUMO4 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins