title: Differences in the contribution of the CTLA4 gene to susceptibility to fulminant and type 1A diabetes in Japanese patients.
abstract: OBJECTIVE
  To examine the contribution of the CTLA4 gene in the susceptibility to fulminant type 1 diabetes and compare it with classic type 1A diabetes.
  
  
  METHODS
  We genotyped the +49G>A and CT60G>A variants of the CTLA4 gene in fulminant type 1 diabetic patients (n = 55), classic type 1A diabetic patients (n = 91), and healthy control subjects (n = 369). We also assessed serum levels of the soluble form of CTLA4 (sCTLA4).
  
  
  RESULTS
  The +49GG and CT60GG genotypes were associated with type 1A diabetes (P < 0.001). In contrast, the CT60AA genotype, but not the +49G>A variation, was associated with fulminant type 1 diabetes (P < 0.05), especially in patients carrying HLA-DR4 (P < 0.01). Serum levels of sCTLA4 were significantly decreased in patients with fulminant type 1 diabetes (P < 0.05).
  
  
  CONCLUSIONS
  These results suggest that CTLA4 CT60 affects the genetic susceptibility to fulminant type 1 diabetes. Furthermore, the contribution of CTLA4 to disease susceptibility is distinct between fulminant type 1 diabetes and classic type 1A diabetes.
authors.affiliation: Department of Metabolism, Diabetes and Clinical Nutrition, Nagasaki University Hospital of Medicine and Dentistry, Nagasaki, Japan. eijikawa@nagasaki-u.ac.jp
authors.forename: Eiji
authors.initials: E
authors.lastname: Kawasaki
authors.forename: Akihisa
authors.initials: A
authors.lastname: Imagawa
authors.forename: Hideichi
authors.initials: H
authors.lastname: Makino
authors.forename: Miho
authors.initials: M
authors.lastname: Uga
authors.forename: Norio
authors.initials: N
authors.lastname: Abiru
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Uchigata
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015703:Antigens, CD / Q000235:genetics*; D060908:CTLA-4 Antigen; D003922:Diabetes Mellitus, Type 1 / Q000145:classification / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human