title: [+49 A/G genetic polymorphism of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) in type 7 diabetes: association with autoantibodies and cytokines].
abstract: BACKGROUND
  Cytotoxic T lymphocyte associated antigen 4 (CTLA-4) has been one ofthe non HLA genes more commonly studied in type 1 diabetes mellitus (TID). CTLA-4 is a co-stimulation protein that has a key role in the negative regulation ofT cells and is related with a functional cytokine imbalance, generating a T helper (Th) 1 over Th2 dominance.
  
  
  OBJECTIVE
  To analyze the association of +49 A/G polymorphism of CTLA-4 and its relationship with autoantibodies and cytokine expression in recently diagnosed TID patients.
  
  
  METHODS
  CTLA-4 genetic variants and auto-antibody levéis were studied in 260 chiídren with TID and 255 healthy chiídren matched by age and gender +49 A/G polymorphism of CTLA-4 was studied by polymerase chain reaction and restriction fragmentpolymorphism (PCR-RFLP). Autoantibody levéis were measured by conventional ELISA. A panel of60 cytokines was studied simultaneously by serum array analysis in 15 TID and 15 healthy controls stratified according CTLA-4 genotype.
  
  
  RESULTS
  The +49 A/G genetic frequency was similar in TID cases and healthy chiídren. A positive anti-GAD65 and anti-IA-2 level was observed in 673% of TID group. This percentage was increased among GG carriers (79.4% to GAD65 and 70.6% to IA-2). Finally, TID patients carrying this genotype showed a high expression of interleukin 2, 10, tumor necrosis factor alpha and interferon gamma.
  
  
  CONCLUSIONS
  The +49 A/G polymorphism of CTLA-4 was similar in diabetic and control chiídren. Among patients with TID and carriers of GG genotype, a higher frequency of anti-GAD65 and a preferential Thl cytokine expression profile was observed.
authors.affiliation: Laboratorio de Epidemiología Nutricional, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Santiago, Chile. fperez@inta.cl
authors.forename: Francisco
authors.initials: F
authors.lastname: Pérez B
authors.forename: Ethel
authors.initials: E
authors.lastname: Codner D
authors.forename: Bárbara
authors.initials: B
authors.lastname: Angel B
authors.forename: Iván
authors.initials: I
authors.lastname: Balic N
authors.forename: Elena
authors.initials: E
authors.lastname: Carrasco P
mesh_terms: D000293:Adolescent; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D002648:Child; D016207:Cytokines / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines