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

• Published in: Human immunology 2010-07, Vol.71 (7), p.692-696
• Main Authors: Vallinoto, Antonio C.R, Graça, Ednelza S, Araújo, Mauro S, Azevedo, Vânia N, Cayres-Vallinoto, Izaura, Machado, Luiz Fernando A, Ishak, Marluisa O.G, Ishak, Ricardo
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Brazil; Cytokines; Female; Gene Frequency - genetics; Genetic polymorphism; Genetic Predisposition to Disease - genetics; Genotype; Heterozygote; Homozygote; Humans; IFN-γ; Interferon-gamma - blood; Interferon-gamma - genetics; M. tuberculosis; Male; Mycobacterium tuberculosis; Polymorphism, Single Nucleotide - genetics; Tuberculosis - blood; Tuberculosis - genetics; Tuberculosis, Pulmonary - blood; Tuberculosis, Pulmonary - genetics
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2010.03.008

Abstract Regarding the importance of interferon-γ (IFN-γ) in protective immunity against Mycobacterium tuberculosis and the functional role of IFNG +874T/A single nucleotide polymorphism (SNP) in the IFN-γ 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-γ 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-γ 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-γ 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.