POLIMORFISMO + 49 A/G DEL GEN DEL ANTIGENO 4 DEL LINFOCITO T CITOTOXICO (CTLA-4) EN LA DIABETES TIPO 1: ASOCIACION CON PERFIL DE ANTICUERPOS Y CITOQUINAS
Resumen
Type 1 diabetes (T1D) is an autoimmune disease that involves genetic and environmental factors. The cytotoxic T lymphocyte associate antigen 4 (CTLA4) has been one of the non HLA genes more frequently studied in T1D. CTLA-4 is a costimulation protein that has a key role in the negative regulation of T cells and has been related with a functional cytokines imbalance, generating a Th1 over Th2 dominance. The aim of this study was to analyse the association of +49 A/G polymorphism of CTLA-4 with T1D and its relationship with autoantibodies and cytokines expression in T1D patients with recent diagnosis. Patients and Methods: CTLA-4 genetic variant and auto-antibodies levels were studied in 260 T1D children and 255 healthy children, both groups were matched age and gender. +49 A/G polymorphism of CTLA-4 was studied by PCR-RFLPs. Autoantibodies levels were measured by conventional ELISA. A panel of 60 cytokines was studied simultaneously by serum array analysis in 15 T1D and 15 healthy controls stratified according CTLA-4 genotype. Results: The +49 A/G genetic frequency was similar in T1D cases and healthy children. A positive anti-GAD65 and anti-IA-2 level was observed in 67.3 % of T1D group. This percentage was increased among GG carriers (79.4 % to GAD65 and 70.6 % to IA-2). Finally, the T1D patients carries of this genotype shown high expression of IL-2, IL-10, TNF? and INF? cytokines. Conclusion: The +49A/G polymorphism of CTLA-4 was similar in both groups. In T1D patient’s carriers of GG genotype a higher frequency of anti-GAD65 (79. 4 %) and a preferential Th1 cytokines expression profile was observed.
