Differential combination of cytokine and interferon- γ +874 T/A polymorphisms determines disease severity in pulmonary tuberculosis.

<h4>Background</h4>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...

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Autores principales:	Ambreen Ansari, Zahra Hasan, Ghaffar Dawood, Rabia Hussain
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c7b9f3fc008746c6b230d0ef30f9b9d5
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spelling	oai:doaj.org-article:c7b9f3fc008746c6b230d0ef30f9b9d52021-11-18T07:33:28ZDifferential combination of cytokine and interferon- γ +874 T/A polymorphisms determines disease severity in pulmonary tuberculosis.1932-620310.1371/journal.pone.0027848https://doaj.org/article/c7b9f3fc008746c6b230d0ef30f9b9d52011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22140472/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methods and findings</h4>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 χ²) 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).<h4>Conclusion</h4>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.Ambreen AnsariZahra HasanGhaffar DawoodRabia HussainPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27848 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ambreen Ansari Zahra Hasan Ghaffar Dawood Rabia Hussain Differential combination of cytokine and interferon- γ +874 T/A polymorphisms determines disease severity in pulmonary tuberculosis.
description	<h4>Background</h4>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.<h4>Methods and findings</h4>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 χ²) 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).<h4>Conclusion</h4>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.
format	article
author	Ambreen Ansari Zahra Hasan Ghaffar Dawood Rabia Hussain
author_facet	Ambreen Ansari Zahra Hasan Ghaffar Dawood Rabia Hussain
author_sort	Ambreen Ansari
title	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_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_sort	differential combination of cytokine and interferon- γ +874 t/a polymorphisms determines disease severity in pulmonary tuberculosis.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/c7b9f3fc008746c6b230d0ef30f9b9d5
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Differential combination of cytokine and interferon- γ +874 T/A polymorphisms determines disease severity in pulmonary tuberculosis.

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