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Differential Combination of Cytokine and Interferon- γ +874 T/A Polymorphisms Determines Disease Severity in Pulmonary Tuberculosis

BACKGROUND: Mycobacterium tuberculosis infects nearly 1/3 of the world population and this reservoir forms the largest pool from which new cases arise. Among the cytokines, IFN-γ is a key determinant in protection against tuberculosis. Single nucleotide polymorphisms (SNPs) in IFN-γ gene (+874 T/A)...

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Autores principales: Ansari, Ambreen, Hasan, Zahra, Dawood, Ghaffar, Hussain, Rabia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226558/
https://www.ncbi.nlm.nih.gov/pubmed/22140472
http://dx.doi.org/10.1371/journal.pone.0027848
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author Ansari, Ambreen
Hasan, Zahra
Dawood, Ghaffar
Hussain, Rabia
author_facet Ansari, Ambreen
Hasan, Zahra
Dawood, Ghaffar
Hussain, Rabia
author_sort Ansari, Ambreen
collection PubMed
description BACKGROUND: Mycobacterium tuberculosis infects nearly 1/3 of the world population and this reservoir forms the largest pool from which new cases arise. Among the cytokines, IFN-γ is a key determinant in protection against tuberculosis. Single nucleotide polymorphisms (SNPs) in IFN-γ gene (+874 T/A) which determine TT high ((hi)), AA low ((lo)) and TA intermediate ((int)) responder phenotypes have shown variable associations with tuberculosis disease outcome in different ethnic populations. The objective of the current study was to analyze IFN-γ gene combinations with other IFN-γ regulating cytokine genes (IL-10, TNF –α, IL-6) to see the effect of gene- combinations on disease severity outcome in pulmonary tuberculosis. METHODS AND FINDINGS: Study groups comprised of pulmonary TB patients stratified according to lung tissue involvement into mild (Pmd = 74) or advance (Pad = 23) lung disease and compared with healthy controls (TBNA = 166). Genotype analysis was carried out using amplification refractory mutation system-PCR (ARMS-PCR). IFN-γ gene (+874 T/A) functional SNP combinations in TNFα (−308 G/A), IL-10 (−1082 A/G) and IL-6 (−174 G/C) were analyzed. Single gene analysis (Pearson χ(2)) showed a dominant association of IFN-γ TT (hi) genotype (p = 0.001) and T allele (p = 0.001) with mild disease. IFN-γ (lo) -IL-10 (lo) genotype combination was associated with advanced disease (p = 0.002). IFN-γ (hi) –IL-6 (hi) combination was associated with mild disease (p = 0.0005) while IFN-γ (lo) –IL-6 (int) was associated with protection against both forms of pulmonary disease (p = 0.002). CONCLUSION: Our results show that a limited number of IFN-γ gene combinations with other cytokine functional SNPs determine the outcome of disease severity in tuberculosis.
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spelling pubmed-32265582011-12-02 Differential Combination of Cytokine and Interferon- γ +874 T/A Polymorphisms Determines Disease Severity in Pulmonary Tuberculosis Ansari, Ambreen Hasan, Zahra Dawood, Ghaffar Hussain, Rabia PLoS One Research Article BACKGROUND: Mycobacterium tuberculosis infects nearly 1/3 of the world population and this reservoir forms the largest pool from which new cases arise. Among the cytokines, IFN-γ is a key determinant in protection against tuberculosis. Single nucleotide polymorphisms (SNPs) in IFN-γ gene (+874 T/A) which determine TT high ((hi)), AA low ((lo)) and TA intermediate ((int)) responder phenotypes have shown variable associations with tuberculosis disease outcome in different ethnic populations. The objective of the current study was to analyze IFN-γ gene combinations with other IFN-γ regulating cytokine genes (IL-10, TNF –α, IL-6) to see the effect of gene- combinations on disease severity outcome in pulmonary tuberculosis. METHODS AND FINDINGS: Study groups comprised of pulmonary TB patients stratified according to lung tissue involvement into mild (Pmd = 74) or advance (Pad = 23) lung disease and compared with healthy controls (TBNA = 166). Genotype analysis was carried out using amplification refractory mutation system-PCR (ARMS-PCR). IFN-γ gene (+874 T/A) functional SNP combinations in TNFα (−308 G/A), IL-10 (−1082 A/G) and IL-6 (−174 G/C) were analyzed. Single gene analysis (Pearson χ(2)) showed a dominant association of IFN-γ TT (hi) genotype (p = 0.001) and T allele (p = 0.001) with mild disease. IFN-γ (lo) -IL-10 (lo) genotype combination was associated with advanced disease (p = 0.002). IFN-γ (hi) –IL-6 (hi) combination was associated with mild disease (p = 0.0005) while IFN-γ (lo) –IL-6 (int) was associated with protection against both forms of pulmonary disease (p = 0.002). CONCLUSION: Our results show that a limited number of IFN-γ gene combinations with other cytokine functional SNPs determine the outcome of disease severity in tuberculosis. Public Library of Science 2011-11-29 /pmc/articles/PMC3226558/ /pubmed/22140472 http://dx.doi.org/10.1371/journal.pone.0027848 Text en Ansari et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ansari, Ambreen
Hasan, Zahra
Dawood, Ghaffar
Hussain, Rabia
Differential Combination of Cytokine and Interferon- γ +874 T/A Polymorphisms Determines Disease Severity in Pulmonary Tuberculosis
title Differential Combination of Cytokine and Interferon- γ +874 T/A Polymorphisms Determines Disease Severity in Pulmonary Tuberculosis
title_full Differential Combination of Cytokine and Interferon- γ +874 T/A Polymorphisms Determines Disease Severity in Pulmonary Tuberculosis
title_fullStr Differential Combination of Cytokine and Interferon- γ +874 T/A Polymorphisms Determines Disease Severity in Pulmonary Tuberculosis
title_full_unstemmed Differential Combination of Cytokine and Interferon- γ +874 T/A Polymorphisms Determines Disease Severity in Pulmonary Tuberculosis
title_short Differential Combination of Cytokine and Interferon- γ +874 T/A Polymorphisms Determines Disease Severity in Pulmonary Tuberculosis
title_sort differential combination of cytokine and interferon- γ +874 t/a polymorphisms determines disease severity in pulmonary tuberculosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226558/
https://www.ncbi.nlm.nih.gov/pubmed/22140472
http://dx.doi.org/10.1371/journal.pone.0027848
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