title: 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.
authors.affiliation: Virus Laboratory, Institute for Biological Sciences, Federal University of Para, Para, Brazil. vallinoto@ufpa.br
authors.forename: Antonio C R
authors.initials: AC
authors.lastname: Vallinoto
authors.forename: Ednelza S
authors.initials: ES
authors.lastname: Graça
authors.forename: Mauro S
authors.initials: MS
authors.lastname: Araújo
authors.forename: Vânia N
authors.initials: VN
authors.lastname: Azevedo
authors.forename: Izaura
authors.initials: I
authors.lastname: Cayres-Vallinoto
authors.forename: Luiz Fernando A
authors.initials: LF
authors.lastname: Machado
authors.forename: Marluisa O G
authors.initials: MO
authors.lastname: Ishak
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ishak
mesh_terms: D001938:Brazil; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007371:Interferon-gamma / Q000097:blood* / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014376:Tuberculosis / Q000097:blood* / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000235:genetics
chemical_list: D007371:Interferon-gamma