Cytokine gene polymorphisms across tuberculosis clinical spectrum in Pakistani patients.
<h4>Background</h4>Pakistan ranks 7(th) globally in terms of tuberculosis (TB) disease burden (incidence 181/100000 pop./yr; prevalence of 329/pop./yr). Reports from different populations show variable associations of TB susceptibility and severity with cytokine gene polymorphisms. Tuber...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19274101/pdf/?tool=EBI |
| _version_ | 1818826922810933248 |
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| author | Ambreen Ansari Najeeha Talat Bushra Jamil Zahra Hasan Tashmeem Razzaki Ghaffar Dawood Rabia Hussain |
| author_facet | Ambreen Ansari Najeeha Talat Bushra Jamil Zahra Hasan Tashmeem Razzaki Ghaffar Dawood Rabia Hussain |
| author_sort | Ambreen Ansari |
| collection | DOAJ |
| description | <h4>Background</h4>Pakistan ranks 7(th) globally in terms of tuberculosis (TB) disease burden (incidence 181/100000 pop./yr; prevalence of 329/pop./yr). Reports from different populations show variable associations of TB susceptibility and severity with cytokine gene polymorphisms. Tuberculosis clinical severity is multi-factorial and cytokines play a pivotal role in the modulation of disease severity. We have recently reported that the ratio of two key cytokines (IFNgamma and IL10) show significant correlation with the severity spectrum of tuberculosis. The objective of the current study was to analyze the frequency of cytokine gene polymorphisms linked to high and low responder phenotypes (IFNgamma +874 T(hi)-->A(lo) and IL10 -1082 G(lo)-->A(hi)) in tuberculosis patients.<h4>Methods and findings</h4>STUDY GROUPS WERE STRATIFIED ACCORDING TO DISEASE SITE AS WELL AS DISEASE SEVERITY: Pulmonary N = 111 (Minimal, PMN = 19; Moderate, PMD = 63; Advance, PAD = 29); Extra-pulmonary N = 67 (Disseminated DTB = 20, Localized LTB = 47) and compared with healthy controls (TBNA = 188). Genotype analyses were carried out using amplification refractory mutation system-PCR (ARMS-PCR) and stimulated whole blood (WB) culture assay was used for assessing cytokine profiles. Our results suggest that the IFNgamma +874 TT genotype and T allele was overrepresented in PMN (p = 0.01) and PMD (p = 0.02). IFNgamma +874 TT in combination with IL10 GG(lo) genotypes showed the highest association (chi(2) = 6.66, OR = 6.06, 95% CI = 1.31-28.07, p = 0.01). IFNgamma AA(lo) on the other hand in combination with IL10 GG(lo) increased the risk of PAD (OR = 5.26; p = 0.005) and DTB (OR = 3.59; p = 0.045).<h4>Conclusion</h4>These findings are consistent with the role of IL10 in reducing collateral tissue damage and the protective role of IFNgamma in limiting disease in the lung. |
| first_indexed | 2024-12-19T00:35:22Z |
| format | Article |
| id | doaj.art-a8347054f4ac47819c92f572ddf540ef |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T00:35:22Z |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-a8347054f4ac47819c92f572ddf540ef2022-12-21T20:44:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0143e477810.1371/journal.pone.0004778Cytokine gene polymorphisms across tuberculosis clinical spectrum in Pakistani patients.Ambreen AnsariNajeeha TalatBushra JamilZahra HasanTashmeem RazzakiGhaffar DawoodRabia Hussain<h4>Background</h4>Pakistan ranks 7(th) globally in terms of tuberculosis (TB) disease burden (incidence 181/100000 pop./yr; prevalence of 329/pop./yr). Reports from different populations show variable associations of TB susceptibility and severity with cytokine gene polymorphisms. Tuberculosis clinical severity is multi-factorial and cytokines play a pivotal role in the modulation of disease severity. We have recently reported that the ratio of two key cytokines (IFNgamma and IL10) show significant correlation with the severity spectrum of tuberculosis. The objective of the current study was to analyze the frequency of cytokine gene polymorphisms linked to high and low responder phenotypes (IFNgamma +874 T(hi)-->A(lo) and IL10 -1082 G(lo)-->A(hi)) in tuberculosis patients.<h4>Methods and findings</h4>STUDY GROUPS WERE STRATIFIED ACCORDING TO DISEASE SITE AS WELL AS DISEASE SEVERITY: Pulmonary N = 111 (Minimal, PMN = 19; Moderate, PMD = 63; Advance, PAD = 29); Extra-pulmonary N = 67 (Disseminated DTB = 20, Localized LTB = 47) and compared with healthy controls (TBNA = 188). Genotype analyses were carried out using amplification refractory mutation system-PCR (ARMS-PCR) and stimulated whole blood (WB) culture assay was used for assessing cytokine profiles. Our results suggest that the IFNgamma +874 TT genotype and T allele was overrepresented in PMN (p = 0.01) and PMD (p = 0.02). IFNgamma +874 TT in combination with IL10 GG(lo) genotypes showed the highest association (chi(2) = 6.66, OR = 6.06, 95% CI = 1.31-28.07, p = 0.01). IFNgamma AA(lo) on the other hand in combination with IL10 GG(lo) increased the risk of PAD (OR = 5.26; p = 0.005) and DTB (OR = 3.59; p = 0.045).<h4>Conclusion</h4>These findings are consistent with the role of IL10 in reducing collateral tissue damage and the protective role of IFNgamma in limiting disease in the lung.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19274101/pdf/?tool=EBI |
| spellingShingle | Ambreen Ansari Najeeha Talat Bushra Jamil Zahra Hasan Tashmeem Razzaki Ghaffar Dawood Rabia Hussain Cytokine gene polymorphisms across tuberculosis clinical spectrum in Pakistani patients. PLoS ONE |
| title | Cytokine gene polymorphisms across tuberculosis clinical spectrum in Pakistani patients. |
| title_full | Cytokine gene polymorphisms across tuberculosis clinical spectrum in Pakistani patients. |
| title_fullStr | Cytokine gene polymorphisms across tuberculosis clinical spectrum in Pakistani patients. |
| title_full_unstemmed | Cytokine gene polymorphisms across tuberculosis clinical spectrum in Pakistani patients. |
| title_short | Cytokine gene polymorphisms across tuberculosis clinical spectrum in Pakistani patients. |
| title_sort | cytokine gene polymorphisms across tuberculosis clinical spectrum in pakistani patients |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19274101/pdf/?tool=EBI |
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