Análise de polimorfismo no gene CTLA-4 em pacientes com paracoccidioidomicose

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

The CTLA-4 protein is mainly expressed in activated T cells and plays an essential role in the immune response through its regulatory effect on T cell activation. This activity is mediated by the binding of CTLA-4 to molecules of the B7 family that are expressed by antigen-presenting cells. Polymorphisms of the CTLA-4 gene have been correlated to several autoimmune pathologies and, more recently, to neoplastic and infectious illnesses. Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the dimorphic pathogen Paracoccidoides brasiliensis. Its symptoms are associated to various factors, including altered secretion of cytokines, hypergammaglobulinaemia and suppression of cellular immunity. This low responsiveness is also attributed to a higher expression of CTLA-4 in the cells of patients relative to control individuals. This work aimed at studying possible associations of PCM and two single nucleotide polymorphisms (SNPs) of CTLA-4, namely -318C/T in the promoter and +49A/G in exon 1. To this end, 74 PCM patients and 76 controls from different regions of the country had their allelic and genotypic frequencies determined. The comparison of genotypic and allelic frequencies had not showed significant differences between patient and control groups which could associate the CTLA-4 gene SNPs to PCM. The analysis of results concerning haplotypic frequencies revealed a strong linkage disequilibrium (D=1) between SNPs -318 and +49 for the two groups. Nevertheless, the analysis did not reveal significant differences of haplotypic frequencies between groups. Another important focus of study was the genetic structure (ancestry) of the patient and control groups. There was a predominance of European over Amerindian and African ancestries in both groups. From the results it was possible to determine that the population used in this study was genetically homogeneous, and that the absence of an association between polymorphisms of CTLA-4 and PCM cannot be attributed to ancestral bias. This work shows that there is no association of SNPs -318 and +49 of CTLA-4 and resistance and/or susceptibility to paracoccidioidomycosis.

ASSUNTO(S)

genetica paracoccidioidomicose ancestralidade polimorfismos snp -318 snp +49 ctla-4

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