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

Balic, I; Ángel B.; Codner, E; Carrasco, E; Perez-Bravo, F

Abstract

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-?, tumor necrosis factor-a, and transforming growth factor-ß 1 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-a and interferon-? 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. © 2009.

Más información

Título según WOS: Association of CTLA-4 polymorphisms and clinical-immunologic characteristics at onset of type 1 diabetes mellitus in children
Título según SCOPUS: Association of CTLA-4 polymorphisms and clinical-immunologic characteristics at onset of type 1 diabetes mellitus in children
Título de la Revista: HUMAN IMMUNOLOGY
Volumen: 70
Número: 2
Editorial: Elsevier Science Inc.
Fecha de publicación: 2009
Página de inicio: 116
Página final: 120
Idioma: English
URL: http://linkinghub.elsevier.com/retrieve/pii/S019888590800548X
DOI:

10.1016/j.humimm.2008.12.007

Notas: ISI, SCOPUS