Association Between Arg753Gln and Arg677Trp Polymorphisms of TLR2 Gene with Active Pulmonary Tuberculosis in an Indonesian Population

Background: Toll-like receptor is a pattern recognition receptor (PRR) that recognize pathogen-associated molecular pattern (PAMP) in a microorganism. Macrophages recognize the presence of mycobacteria through Toll-Like Receptor 2 (TLR2) and signaling further lead to the production of cytokines, bot...

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Main Authors: Arto Yuwono Soeroto, Zulkarnain Dahlan, Cissy B Kartasasmita, Ida Parwati
Format: Article
Language:English
Published: Interna Publishing 2018-04-01
Series:Acta Medica Indonesiana
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Online Access:https://actamedindones.org/index.php/ijim/article/view/305
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author Arto Yuwono Soeroto
Zulkarnain Dahlan
Cissy B Kartasasmita
Ida Parwati
author_facet Arto Yuwono Soeroto
Zulkarnain Dahlan
Cissy B Kartasasmita
Ida Parwati
author_sort Arto Yuwono Soeroto
collection DOAJ
description Background: Toll-like receptor is a pattern recognition receptor (PRR) that recognize pathogen-associated molecular pattern (PAMP) in a microorganism. Macrophages recognize the presence of mycobacteria through Toll-Like Receptor 2 (TLR2) and signaling further lead to the production of cytokines, both proinflammatory TNF-α, IL-1β, IL-6, IL-12, IL-15, IL-18 and IFN-γ, as well as anti-inflammatory IL4, IL-10 and TGF-β. TLR2 gene polymorphism is strongly determined by ethnicity and geography. Therefore it is necessary to uncovered the existence and association between Arg753Gln and Arg677Trp TLR2 gene polymorphism with TB susceptibility and its underlying mechanisms in Indonesian population in Bandung West Java. Methods: analytical observational study with cross-sectional design was conducted in Hasan Sadikin General Hospital Bandung from April 2011 to May 2012. Study population consisted of active pulmonary TB patient with positive AFB smear and Latent TB  to ascertain previous MTb exposure. Polymorphism of gen Arg753Gln and Arg677Trp gene was determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Plasma levels of IFN-γ, TNF-α, IL-10 and IL-12 were also compared between active and latent TB group. Results: heterozygote Arg753Gln TLR2 gene polymorphism was found in 9 of 86 pulmonary TB subjects (10.5%) but none in the latent TB group. The Arg677Trp polymorphism was not found in both groups. The odds ratio for Arg753Gln existence was 28.07 (p=0.022). No differences in the levels of IFN-γ, TNF-α, IL-10 and IL-12 between active pulmonary TB and latent TB subjects with and without Arg753Gln TLR2 gene polymorphism. Conlusion: Arg753Gln polymorphism of TLR2 gene is a risk factor for active pulmonary TB while Arg677Trp polymorphism is not. The Increased risk is not mediated by the difference in IFN-γ, TNF-α, IL-10 and IL-12 serum levels.
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spelling doaj-art-b17ff660ddc64defb1d1ee9d08e668772025-08-20T02:50:52ZengInterna PublishingActa Medica Indonesiana0125-93262338-27322018-04-01501239Association Between Arg753Gln and Arg677Trp Polymorphisms of TLR2 Gene with Active Pulmonary Tuberculosis in an Indonesian PopulationArto Yuwono Soeroto0Zulkarnain Dahlan1Cissy B Kartasasmita2Ida Parwati3Department of Internal Medicine, Faculty of Medicine Universitas Padjadjaran, Bandung, IndonesiaDepartment of Internal Medicine, Faculty of Medicine Universitas Padjadjaran, Bandung, IndonesiaDepartment of Pediatrics, Faculty of Medicine Universitas Padjadjaran, Bandung, IndonesiaDepartment of Clinical Pathology, Faculty of Medicine Universitas Padjadjaran, Bandung, IndonesiaBackground: Toll-like receptor is a pattern recognition receptor (PRR) that recognize pathogen-associated molecular pattern (PAMP) in a microorganism. Macrophages recognize the presence of mycobacteria through Toll-Like Receptor 2 (TLR2) and signaling further lead to the production of cytokines, both proinflammatory TNF-α, IL-1β, IL-6, IL-12, IL-15, IL-18 and IFN-γ, as well as anti-inflammatory IL4, IL-10 and TGF-β. TLR2 gene polymorphism is strongly determined by ethnicity and geography. Therefore it is necessary to uncovered the existence and association between Arg753Gln and Arg677Trp TLR2 gene polymorphism with TB susceptibility and its underlying mechanisms in Indonesian population in Bandung West Java. Methods: analytical observational study with cross-sectional design was conducted in Hasan Sadikin General Hospital Bandung from April 2011 to May 2012. Study population consisted of active pulmonary TB patient with positive AFB smear and Latent TB  to ascertain previous MTb exposure. Polymorphism of gen Arg753Gln and Arg677Trp gene was determined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Plasma levels of IFN-γ, TNF-α, IL-10 and IL-12 were also compared between active and latent TB group. Results: heterozygote Arg753Gln TLR2 gene polymorphism was found in 9 of 86 pulmonary TB subjects (10.5%) but none in the latent TB group. The Arg677Trp polymorphism was not found in both groups. The odds ratio for Arg753Gln existence was 28.07 (p=0.022). No differences in the levels of IFN-γ, TNF-α, IL-10 and IL-12 between active pulmonary TB and latent TB subjects with and without Arg753Gln TLR2 gene polymorphism. Conlusion: Arg753Gln polymorphism of TLR2 gene is a risk factor for active pulmonary TB while Arg677Trp polymorphism is not. The Increased risk is not mediated by the difference in IFN-γ, TNF-α, IL-10 and IL-12 serum levels.https://actamedindones.org/index.php/ijim/article/view/305TLR2Arg753GlnArg677Trpcytokinestuberculosis
spellingShingle Arto Yuwono Soeroto
Zulkarnain Dahlan
Cissy B Kartasasmita
Ida Parwati
Association Between Arg753Gln and Arg677Trp Polymorphisms of TLR2 Gene with Active Pulmonary Tuberculosis in an Indonesian Population
Acta Medica Indonesiana
TLR2
Arg753Gln
Arg677Trp
cytokines
tuberculosis
title Association Between Arg753Gln and Arg677Trp Polymorphisms of TLR2 Gene with Active Pulmonary Tuberculosis in an Indonesian Population
title_full Association Between Arg753Gln and Arg677Trp Polymorphisms of TLR2 Gene with Active Pulmonary Tuberculosis in an Indonesian Population
title_fullStr Association Between Arg753Gln and Arg677Trp Polymorphisms of TLR2 Gene with Active Pulmonary Tuberculosis in an Indonesian Population
title_full_unstemmed Association Between Arg753Gln and Arg677Trp Polymorphisms of TLR2 Gene with Active Pulmonary Tuberculosis in an Indonesian Population
title_short Association Between Arg753Gln and Arg677Trp Polymorphisms of TLR2 Gene with Active Pulmonary Tuberculosis in an Indonesian Population
title_sort association between arg753gln and arg677trp polymorphisms of tlr2 gene with active pulmonary tuberculosis in an indonesian population
topic TLR2
Arg753Gln
Arg677Trp
cytokines
tuberculosis
url https://actamedindones.org/index.php/ijim/article/view/305
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