IFNG +874T/A polymorphism and cytokine plasma levels are associated with susceptibility to Mycobacterium tuberculosis infection and clinical manifestation of tuberculosis

Abstract

Regarding the importance of interferon-gamma (IFN-gamma) in protective immunity against Mycobacterium tuberculosis and the functional role of IFNG +874T/A single nucleotide polymorphism (SNP) in the IFN-gamma production, the present study investigated the relationship of this genetic polymorphism with susceptibility to tuberculosis (TB). A total of 129 patients with pulmonary tuberculosis (PTB), 33 with extrapulmonary tuberculosis (EPTB), and 156 control subjects were studied. Blood samples were drawn and plasma was used to measure IFN-gamma serum concentration by enzyme-linked immunoassay. DNA samples were extracted from leukocytes and used to investigate +874T/A polymorphism in IFNG gene using allele-specific oligonucleotide-polymerase chain reaction. An association between the presence of the allele +874A and the genotype +874AA with the active tuberculosis was found (p < 0.0001, 95% confidence interval = 1.64-3.22), at the same time that allele + 874T and genotype +874T/T were more frequent in the control group. The average plasma concentration of IFN-gamma among patients with tuberculosis was significantly lower than in the control group, and were lower in the EPTB group than in the group with PTB, suggesting a relationship of low plasma levels of this cytokine with active tuberculosis and the progression to more serious forms of the disease. Furthermore, we observed the association of the +874T/T and +874A/A genotypes with high and low IFN-gamma plasma concentrations, respectively, both in TB patients and in the control groups. Thus our findings suggest an association of the IFNG +874T/A polymorphism with susceptibility to M. tuberculosis infection in the studied population.