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

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Abstract

Several genetic cytokine gene variants have been associated with host susceptibility to infectious diseases, including tuberculosis. Based upon the importance of IFN-γ in protective immunity against Mycobacterium tuberculosis, and the functional role of the IFN-γ + 874T/A single nucleotide polymorphism in IFN-γ 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-γ producer allele with tuberculosis occurrence. Using multivariable logistic regression models, genotype and allele frequencies of the mutant + 874A (low IFN-γ 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-γ gene polymorphism is associated with tuberculosis in different populations.

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Acknowledgements

We thank the staff of the Tuberculosis Control Program from the Thoracic Diseases Institute, University Hospital Clementino Fraga Filho (HUCFF)/Federal University of Rio de Janeiro (UFRJ), Tropical Disease Hospital Anuar Auad. Goiás state and Santa Maria State Hospital Rio the Janeiro. T.H.M. Ottenhoff received grants from the EU and from the Dutch Government (NWO). This work was supported by CNPq Millennium Institute of Science (Brazilian Ministry of Science and Technology) grant number 62.0055/01-4, FAPERJ E-26/172.336/2000 and FAPERJ E –26 152 .441/2002.

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Authors and Affiliations

  1. Hospital Complex-HUCFF-IDT Complex-Federal University of Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco 255, Ilha do Fundao, Rio de Janeiro, 21941-590, Brazil

    Lucia H. L. V. Amim, Joseane Fonseca-Costa, Carla S. Loredo, Fernanda C. Q. Mello, Martha M. Oliveira, José R. Lapa e Silva & Afrânio L. Kritski

  2. Department of Epidemiology and Quantitative Methods in Health, National School of Public Health, Rua Leopoldo Bulhões 1.480, Manguinhos, Fiocruz, Rio de Janeiro, Brazil

    Antonio G. Pacheco

  3. Anuar Auad Infectious Disease Reference Hospital, Av. do Contorno, s/n, Goiânia, 74853-400, Brazil

    Marcelo F. Rabahi

  4. Santa Maria State Hospital, Est Rio Pequeno, 656, Rio de Janeiro, 22723-195, Brazil

    Maria H. Melo & Fernando C. V. Ribeiro

  5. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands

    Tom H. Ottenhoff

  6. Laboratory of Molecular Biology Applied to Mycobacteria, Department of Mycobacteriosis, IOC/Fiocruz, Av Brasil, 4365, Rio de Janeiro, 21040-900, Brazil

    Adalberto R. Santos

Authors
  1. Lucia H. L. V. Amim
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  2. Antonio G. Pacheco
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  3. Joseane Fonseca-Costa
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  4. Carla S. Loredo
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  5. Marcelo F. Rabahi
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  6. Maria H. Melo
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  7. Fernando C. V. Ribeiro
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  8. Fernanda C. Q. Mello
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  9. Martha M. Oliveira
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  10. José R. Lapa e Silva
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  11. Tom H. Ottenhoff
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  12. Afrânio L. Kritski
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  13. Adalberto R. Santos
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Corresponding author

Correspondence to Adalberto R. Santos.

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Amim, L.H.L.V., Pacheco, A.G., Fonseca-Costa, J. et al. Role of IFN-γ +874 T/A single nucleotide polymorphism in the tuberculosis outcome among Brazilians subjects. Mol Biol Rep 35, 563–566 (2008). https://doi.org/10.1007/s11033-007-9123-1

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  • DOI: https://doi.org/10.1007/s11033-007-9123-1

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