Caracterização dos níveis plasmáticos e do polimorfismo +874T/A no gene IFN-γ em pacientes com diferentes formas clínicas da tuberculose

Abstract

Regarding the importance of interferon gamma (IFN-γ) in protective immunity against Mycobacterium tuberculosis and the functional role of the single nucleotide polymorphism (SNP) IFNG +874T/A in the IFN-γ production, in the present study, it was investigated the relationship of this genetic polymorphism with susceptibility to tuberculosis. A total of 129 subjects with pulmonary TB (TBP), 33 with extrapulmonary tuberculosis (TBEP) and 156 control group were investigated. Five microliters of blood sample was collected and the plasma was used to measure IFN-g serum concentration by enzyme-linked immunoassay. DNA samples were extracted from leucocytes and used to investigate the polymorphism +874T/A in the IFN-g gene using ASO-PCR (allele specific oligonucleotide - polymerase chain reaction). It was found an association between the presence of the allele +874 A and the genotype +874 AA with the active tuberculosis (p<0.0001, CI = 95%, 1.64 - 3.22), at the same time that, the allele + 874T and genotype +874 TT were more frequent in the control group. The average IFN-g plasma concentrations in patient was significantly lower than that one observed in the control group, as well it was lower in the group with TBEP than in the group with TBP, suggesting a relationship of the low serum levels of this cytokine with the active tuberculosis and the progression to more serious forms of the disease. Furthermore, we observed the association of the +874 TT and +874 AA genotypes with high and low concentrations of IFN-γ, respectively, both in TB patients and control groups. Thus, the results suggest an association of polymorphism +874T/A with the susceptibility to M. tuberculosis infection in the studied population.