Role of IFN-gamma +874 T/A single nucleotide polymorphism in the tuberculosis outcome among Brazilians subjects.

Abstract

Several genetic cytokine gene variants have been associated with host susceptibility to infectious diseases, including tuberculosis. Based upon the importance of IFN-gamma in protective immunity against Mycobacterium tuberculosis, and the functional role of the IFN-gamma + 874T/A single nucleotide polymorphism in IFN-gamma production, we genotyped 93 Brazilian tuberculosis patients and 266 asymptomatic health care workers, including 150 individuals with a positive tuberculin skin test, and analyzed the possible association of the +874A low IFN-gamma producer allele with tuberculosis occurrence. Using multivariable logistic regression models, genotype and allele frequencies of the mutant + 874A (low IFN-gamma producer) allele were significantly associated with tuberculosis disease. Heterozygous carriers had a 25% increased chance, while individuals presenting the A/A homozygous genotype had an over two-fold risk of having active tuberculosis (95% CI, 1.16-5.91, P = 0.03). Despite the mixed ethnicity observed in Brazilian populations, the present data agree with observations reported in other populations and thus demonstrate that the functional +874T/A IFN-gamma gene polymorphism is associated with tuberculosis in different populations.