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Polimorfismo +49 A/G del gen del antígeno 4 del linfocito T citotóxico (CTLA-4) en la diabetes tipo 1: Asociación con el perfil de anticuerpos y citoquinas

    1. [1] Universidad de Chile

      Universidad de Chile

      Santiago, Chile

    2. [2] Hospital San Juan de Dios

      Hospital San Juan de Dios

      Santiago, Chile

  • Localización: Revista Médica de Chile, ISSN-e 0034-9887, Vol. 137, Nº. 3, 2009, págs. 321-328
  • Idioma: español
  • Títulos paralelos:
    • +49 A/G genetic polymorphism of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) in type 7 diabetes: Association with autoantibodies and cytokines
  • Enlaces
  • Resumen
    • 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. Aim: 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. Patients and 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.

Los metadatos del artículo han sido obtenidos de SciELO Chile

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