Association of CTLA-4 polymorphisms and clinical-immunologic characteristics at onset of type 1 diabetes mellitus in children

Iván Balic, Bárbara Angel, Ethel Codner, Elena Carrasco, Francisco Pérez-Bravo

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40 Citations (Scopus)


CTLA-4 is a homeostatic regulator of T cell activation and is believed to play a critical role in immune tolerance. Polymorphisms in the CTLA-4 promoter (-318C/T) and in exon 1 (+49 A/G) were analyzed in 300 Chilean patients with type 1 diabetes mellitus (T1D) and 310 healthy children by polymerase chain reaction-restriction fragment length polymorphism. The effect of CTLA-4 allele and haplotype frequencies on the interferon-γ, tumor necrosis factor-α, and transforming growth factor-β1 levels and the presence in serum of GAD65 and IA-2 autoantibodies at the onset of T1D was evaluated. The distribution of the CTLA-4 allele and genotype frequencies was found to be similar in patients and control children. However, among the T1D patients' carriers of GG genotype on CTLA-4 gene a higher frequency of anti-GAD65 autoantibodies (87.2%) was observed. On the other hand, higher ketoacidosis at onset, younger age at onset, and higher levels of tumor necrosis factor-α and interferon-γ were observed in T1D patients carriers of G allele in comparison with the carriers of AA genotype. In conclusion, the result of this study showed that CTLA-4 +49 A/G and -318 C/T polymorphisms were not linked with a higher genetic risk for T1D. However, the presence of a GG genotype or G allele dosage was associated with a younger age of onset, higher prevalence of ketoacidosis at the moment of diagnosis and positive anti-GAD65 serum autoantibodies.

Original languageEnglish
Pages (from-to)116-120
Number of pages5
JournalHuman Immunology
Issue number2
Publication statusPublished - Feb 2009


  • Autoantibodies
  • CTLA-4 polymorphism
  • Cytokines
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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