Skip to main content
Erschienen in: Lung 3/2009

01.06.2009

Toll-Like Receptor 2 Gene Polymorphisms Arg677Trp and Arg753Gln in Chronic Obstructive Pulmonary Disease

verfasst von: Stefan Pabst, Vildan Yenice, Martina Lennarz, Izabela Tuleta, Georg Nickenig, Adrian Gillissen, Christian Grohé

Erschienen in: Lung | Ausgabe 3/2009

Einloggen, um Zugang zu erhalten

Abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide, with a continually rising mortality rate. As COPD is driven by abnormal pulmonary and systemic inflammation, Toll-like receptors (TLRs) seem to be important. TLRs play a key role in innate response, and in particular TLR2 gene polymorphisms Arg677Trp and Arg753Gln have been linked to an increased risk of infection. The purpose of this study was to investigate whether there is a link between polymorphisms in TLR2 and the onset or course of COPD. We analyzed 149 Caucasian COPD patients and 150 healthy individuals by using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis. To further characterize the disease, patients were classified according to GOLD and divided into two subgroups comprising a stable (60/149) course and an unstable (89/149) course. The TLR2 Arg677Trp mutant allele was not found in any of the subjects. With a prevalence of 8.72% (13/149) for TLR2 Arg753Gln, the patients did not differ from the controls, with a prevalence of 10.67% (16/150). No significant difference was apparent (P = 0.571). None of the individuals showed homozygosity for TLR2 Arg753Gln. With regard to the course of COPD, the prevalence of TLR2 Arg753Gln in the control group did not differ significantly either from the stable subgroup (P = 0.196) or from the unstable subgroup (P = 0.891). Our results suggest that there is no association of the TLR2 polymorphisms Arg677Trp and Arg753Gln with either the onset or the course of COPD.
Literatur
1.
Zurück zum Zitat Monso E, Rosell A, Bonet G, Manterola J, Cardona PJ, Ruiz J, Morera J (1999) Risk factors for lower airway bacterial colonization in chronic bronchitis. Eur Respir J 13:338–348PubMedCrossRef Monso E, Rosell A, Bonet G, Manterola J, Cardona PJ, Ruiz J, Morera J (1999) Risk factors for lower airway bacterial colonization in chronic bronchitis. Eur Respir J 13:338–348PubMedCrossRef
2.
Zurück zum Zitat The COPD guidelines group of the standards of care committee of the BTS (1997) BTS guidelines for the management of chronic obstructive pulmonary disease. Thorax 52(Suppl 5):S1–S28 The COPD guidelines group of the standards of care committee of the BTS (1997) BTS guidelines for the management of chronic obstructive pulmonary disease. Thorax 52(Suppl 5):S1–S28
3.
Zurück zum Zitat McCloskey SC, Patel BD, Hinchliffe SJ, Reid ED, Wareham NJ, Lomas DA (2001) Siblings of patients with severe chronic obstructive pulmonary disease have a significant risk of airflow obstruction. Am J Respir Crit Care Med 164:1419–1424PubMed McCloskey SC, Patel BD, Hinchliffe SJ, Reid ED, Wareham NJ, Lomas DA (2001) Siblings of patients with severe chronic obstructive pulmonary disease have a significant risk of airflow obstruction. Am J Respir Crit Care Med 164:1419–1424PubMed
4.
Zurück zum Zitat Burge PS, Calverley PM, Jones PW, Spencer S, Anderson JA, Maslen TK (2000) Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ 320:1297–1303PubMedCrossRef Burge PS, Calverley PM, Jones PW, Spencer S, Anderson JA, Maslen TK (2000) Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ 320:1297–1303PubMedCrossRef
5.
Zurück zum Zitat Burge S, Wedzicha JA (2003) COPD exacerbations: definitions and classifications. Eur Respir J 21(Suppl 41):46–53CrossRef Burge S, Wedzicha JA (2003) COPD exacerbations: definitions and classifications. Eur Respir J 21(Suppl 41):46–53CrossRef
6.
Zurück zum Zitat Donaldson GC, Seemungal TA, Bhowmilk A, Wedzicha JA (2002) Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 57:847–852PubMedCrossRef Donaldson GC, Seemungal TA, Bhowmilk A, Wedzicha JA (2002) Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 57:847–852PubMedCrossRef
7.
Zurück zum Zitat Sethi S, Muscarella K, Evans N, Klingman KL, Grant BJB, Murphy TF (2000) Airway inflammation and etiology of acute exacerbations of chronic bronchitis. Chest 118:1557–1565PubMedCrossRef Sethi S, Muscarella K, Evans N, Klingman KL, Grant BJB, Murphy TF (2000) Airway inflammation and etiology of acute exacerbations of chronic bronchitis. Chest 118:1557–1565PubMedCrossRef
8.
Zurück zum Zitat Medzhitov R, Preston-Hurlburt P, Janeway CA Jr (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388:394–397PubMedCrossRef Medzhitov R, Preston-Hurlburt P, Janeway CA Jr (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388:394–397PubMedCrossRef
9.
Zurück zum Zitat Underhill DM, Ozinsky A (2002) Toll-like receptors: key mediators of microbe detection. Curr Opin Immunol 14:103–110PubMedCrossRef Underhill DM, Ozinsky A (2002) Toll-like receptors: key mediators of microbe detection. Curr Opin Immunol 14:103–110PubMedCrossRef
10.
Zurück zum Zitat Chaudhuri N, Dower SK, Whyte MKB, Sabroe I (2005) Toll-like receptors and chronic lung disease. Clin Sci 109:125–133PubMedCrossRef Chaudhuri N, Dower SK, Whyte MKB, Sabroe I (2005) Toll-like receptors and chronic lung disease. Clin Sci 109:125–133PubMedCrossRef
11.
Zurück zum Zitat Pierik M, Joossens S, Van Steen K, Van Schuerbeek N, Vlietinck R, Rutgeerts P, Vermeire S (2006) Toll-like receptor-1, -2, and -6 polymorphisms influence disease extension in inflammatory bowel diseases. Inflamm Bowel Dis 12:1–8PubMedCrossRef Pierik M, Joossens S, Van Steen K, Van Schuerbeek N, Vlietinck R, Rutgeerts P, Vermeire S (2006) Toll-like receptor-1, -2, and -6 polymorphisms influence disease extension in inflammatory bowel diseases. Inflamm Bowel Dis 12:1–8PubMedCrossRef
12.
Zurück zum Zitat Texereau J, Chiche JD, Taylor W, Choukroun G, Comba B, Mira JB (2005) The importance of Toll-like receptor 2 polymorphisms in severe infections. Clin Iinfect Dis 41(Suppl 7):S408–S415CrossRef Texereau J, Chiche JD, Taylor W, Choukroun G, Comba B, Mira JB (2005) The importance of Toll-like receptor 2 polymorphisms in severe infections. Clin Iinfect Dis 41(Suppl 7):S408–S415CrossRef
13.
Zurück zum Zitat Rock FL, Hardiman G, Timans JC, Kastelein RA, Bazan JF (1998) A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci U S A 95:588–593PubMedCrossRef Rock FL, Hardiman G, Timans JC, Kastelein RA, Bazan JF (1998) A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci U S A 95:588–593PubMedCrossRef
14.
Zurück zum Zitat Droemann D, Goldmann T, Branscheid D, Clark R, Dalhoff K, Zabel P, Vollmer E (2003) Toll-like receptor 2 is expressed by alveolar epithelial cells type II and macrophages in the human lung. Histochem Cell Biol 119:103–108PubMed Droemann D, Goldmann T, Branscheid D, Clark R, Dalhoff K, Zabel P, Vollmer E (2003) Toll-like receptor 2 is expressed by alveolar epithelial cells type II and macrophages in the human lung. Histochem Cell Biol 119:103–108PubMed
15.
Zurück zum Zitat Van der Pouw Kraan TC, Kucukaycan M, Bakker AM, Baggen JM, van der Zee JS, Dentener MA, Wouters EF, Verweij CL (2002) Chronic obstructive pulmonary disease is associated with the -1055 IL-13 promoter polymorphism. Genes Immun 3:436–439PubMedCrossRef Van der Pouw Kraan TC, Kucukaycan M, Bakker AM, Baggen JM, van der Zee JS, Dentener MA, Wouters EF, Verweij CL (2002) Chronic obstructive pulmonary disease is associated with the -1055 IL-13 promoter polymorphism. Genes Immun 3:436–439PubMedCrossRef
16.
Zurück zum Zitat Hu RC, Xu YJ, Zhang ZX, Xie JG (2003) Polymorphism of interleukin-10 gene promoter and its association with susceptibility to chronic obstructive pulmonary disease in Chinese Han people. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 20:504–507PubMed Hu RC, Xu YJ, Zhang ZX, Xie JG (2003) Polymorphism of interleukin-10 gene promoter and its association with susceptibility to chronic obstructive pulmonary disease in Chinese Han people. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 20:504–507PubMed
17.
Zurück zum Zitat Stemmler S, Arinir U, Klein W, Rohde G, Hoffjan S, Wirkus N, Reinitz-Rademacher K, Bufe A, Schultze-Werninghaus G, Epplen JT (2005) Association of interleukin-8 receptor alpha polymorphisms with chronic obstructive pulmonary disease and asthma. Genes Immun 6:225–230PubMedCrossRef Stemmler S, Arinir U, Klein W, Rohde G, Hoffjan S, Wirkus N, Reinitz-Rademacher K, Bufe A, Schultze-Werninghaus G, Epplen JT (2005) Association of interleukin-8 receptor alpha polymorphisms with chronic obstructive pulmonary disease and asthma. Genes Immun 6:225–230PubMedCrossRef
18.
Zurück zum Zitat Celli BR, MacNee W, ATS/ERS Task Force (2004) Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 23:932–946PubMedCrossRef Celli BR, MacNee W, ATS/ERS Task Force (2004) Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 23:932–946PubMedCrossRef
19.
Zurück zum Zitat Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215PubMedCrossRef Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215PubMedCrossRef
20.
Zurück zum Zitat Pabst S, Baumgarten G, Stremmel A, Lennarz M, Knufermann P, Gillissen A, Vetter H, Grohe C (2006) Toll-like receptor (TLR) 4 polymorphisms are associated with a chronic course of sarcoidosis. Clin Exp Immunol 143:420–426PubMedCrossRef Pabst S, Baumgarten G, Stremmel A, Lennarz M, Knufermann P, Gillissen A, Vetter H, Grohe C (2006) Toll-like receptor (TLR) 4 polymorphisms are associated with a chronic course of sarcoidosis. Clin Exp Immunol 143:420–426PubMedCrossRef
21.
Zurück zum Zitat Folwaczny M, Glas J, Török HP, Limbersky O, Folwaczny C (2004) Toll-like receptor (TLR) 2 and 4 mutations in periodontal disease. Clin Exp Immunol 135:330–335PubMedCrossRef Folwaczny M, Glas J, Török HP, Limbersky O, Folwaczny C (2004) Toll-like receptor (TLR) 2 and 4 mutations in periodontal disease. Clin Exp Immunol 135:330–335PubMedCrossRef
22.
Zurück zum Zitat Sasieni PD (2997) From genotypes to genes: doubling the sample size. Biometrics 53:1253–1261CrossRef Sasieni PD (2997) From genotypes to genes: doubling the sample size. Biometrics 53:1253–1261CrossRef
23.
Zurück zum Zitat Bochud PY, Hawn TR, Aderem A (2003) Cutting edge: A Toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediate mycobacterial signalling. J Immunol 170:3451–3454PubMed Bochud PY, Hawn TR, Aderem A (2003) Cutting edge: A Toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediate mycobacterial signalling. J Immunol 170:3451–3454PubMed
24.
Zurück zum Zitat Kang TJ, Chae GT (2001) Detection of Toll-like receptor 2 (TLR2) mutation in the lepromatous leprosy patients. FEMS Immunol Med Microbiol 31:53–58PubMedCrossRef Kang TJ, Chae GT (2001) Detection of Toll-like receptor 2 (TLR2) mutation in the lepromatous leprosy patients. FEMS Immunol Med Microbiol 31:53–58PubMedCrossRef
25.
Zurück zum Zitat Ben-Ali M, Barbouche MR, Bousnina S, Chabbou A, Dellgi K (2004) Toll-like receptor 2 Arg677Trp polymorphism is associated with susceptibility to tuberculosis in Tunisian patients. Clin Diagn Lab Immunol 11:625–626PubMed Ben-Ali M, Barbouche MR, Bousnina S, Chabbou A, Dellgi K (2004) Toll-like receptor 2 Arg677Trp polymorphism is associated with susceptibility to tuberculosis in Tunisian patients. Clin Diagn Lab Immunol 11:625–626PubMed
26.
Zurück zum Zitat Malhotra D, Relhan V, Reddy BSN, Bamezai R (2005) TLR2 Arg677Trp polymorphism in leprosy: revisited. Hum Genet 116:413–415PubMedCrossRef Malhotra D, Relhan V, Reddy BSN, Bamezai R (2005) TLR2 Arg677Trp polymorphism in leprosy: revisited. Hum Genet 116:413–415PubMedCrossRef
27.
Zurück zum Zitat Schroeder NWJ, Hermann C, Hamann L, Goebel UB, Hartung T, Schuhmann RR (2003) High frequency of polymorphism Arg753Gln of the Toll-like receptor-2 gene detected by a novel allele-specific PCR. J Mol Med 81:368–372CrossRef Schroeder NWJ, Hermann C, Hamann L, Goebel UB, Hartung T, Schuhmann RR (2003) High frequency of polymorphism Arg753Gln of the Toll-like receptor-2 gene detected by a novel allele-specific PCR. J Mol Med 81:368–372CrossRef
28.
Zurück zum Zitat Ogus AC, Yoldas B, Ozdemir T, Uguz A, Olcen S, Keser I, Coskun M, Cilli A, Yegin O (2004) The Arg753Gln polymorphism of the human Toll-like receptor 2 gene in tuberculosis disease. Eur Respir J 23:219–223PubMedCrossRef Ogus AC, Yoldas B, Ozdemir T, Uguz A, Olcen S, Keser I, Coskun M, Cilli A, Yegin O (2004) The Arg753Gln polymorphism of the human Toll-like receptor 2 gene in tuberculosis disease. Eur Respir J 23:219–223PubMedCrossRef
29.
Zurück zum Zitat Schroder NW, Diterich I, Zinke A, Eckert J, Draing C, von Baehr V, Hassler D, Priem S, Hahn K, Michelsen KS, Hartung T, Burmester GR, Gobel UB, Hermann C, Schumann RR (2005) Heterozygous Arg753Gln polymorphism of human TLR-2 impairs immune activation by Borrelia burgdorferi and protects from late stage Lyme disease. J Immunol 175:2534–2540PubMed Schroder NW, Diterich I, Zinke A, Eckert J, Draing C, von Baehr V, Hassler D, Priem S, Hahn K, Michelsen KS, Hartung T, Burmester GR, Gobel UB, Hermann C, Schumann RR (2005) Heterozygous Arg753Gln polymorphism of human TLR-2 impairs immune activation by Borrelia burgdorferi and protects from late stage Lyme disease. J Immunol 175:2534–2540PubMed
30.
Zurück zum Zitat Moore CE, Segal S, Berendt AR, Hill AVS, Day NPJ (2004) Lack of association between Toll-like receptor 2 polymorphisms and susceptibility to severe disease caused by Staphylococcus aureus. Clin Diagn Lab Immunol 11:1194–1197PubMed Moore CE, Segal S, Berendt AR, Hill AVS, Day NPJ (2004) Lack of association between Toll-like receptor 2 polymorphisms and susceptibility to severe disease caused by Staphylococcus aureus. Clin Diagn Lab Immunol 11:1194–1197PubMed
31.
Zurück zum Zitat Ugenskiene R, Sanak M, Sakalauskas R, Szczeklik A (2005) Genetic polymorphisms in chronic obstructive pulmonary disease. Medicina (Kaunas) 41:17–22 Ugenskiene R, Sanak M, Sakalauskas R, Szczeklik A (2005) Genetic polymorphisms in chronic obstructive pulmonary disease. Medicina (Kaunas) 41:17–22
32.
Zurück zum Zitat Pons J, Sauleda J, Regueiro V, Santos C, Lopez M, Ferrer J, Agusti AG, Bengoechea JA (2006) Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease. Respir Res 7:64PubMedCrossRef Pons J, Sauleda J, Regueiro V, Santos C, Lopez M, Ferrer J, Agusti AG, Bengoechea JA (2006) Expression of Toll-like receptor 2 is up-regulated in monocytes from patients with chronic obstructive pulmonary disease. Respir Res 7:64PubMedCrossRef
33.
Zurück zum Zitat Shuto T, Imasato A, Jono H, Sakai A, Xu H, Watanabe T, Rixter DD, Kai H, Andalibi A, Linthicum F, Guan YL, Han J, Cato AC, Lim DJ, Akira S, Li JD (2002) Glucocorticoids synergistically enhance non-typeable Haemophilus influenzae-induced Toll-like receptor 2 expression via a negative cross-talk with p38 MAP kinase. J Biol Chem 277:17263–17270PubMedCrossRef Shuto T, Imasato A, Jono H, Sakai A, Xu H, Watanabe T, Rixter DD, Kai H, Andalibi A, Linthicum F, Guan YL, Han J, Cato AC, Lim DJ, Akira S, Li JD (2002) Glucocorticoids synergistically enhance non-typeable Haemophilus influenzae-induced Toll-like receptor 2 expression via a negative cross-talk with p38 MAP kinase. J Biol Chem 277:17263–17270PubMedCrossRef
Metadaten
Titel
Toll-Like Receptor 2 Gene Polymorphisms Arg677Trp and Arg753Gln in Chronic Obstructive Pulmonary Disease
verfasst von
Stefan Pabst
Vildan Yenice
Martina Lennarz
Izabela Tuleta
Georg Nickenig
Adrian Gillissen
Christian Grohé
Publikationsdatum
01.06.2009
Verlag
Springer-Verlag
Erschienen in
Lung / Ausgabe 3/2009
Print ISSN: 0341-2040
Elektronische ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-009-9144-8

Weitere Artikel der Ausgabe 3/2009

Lung 3/2009 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

RAS-Blocker bei Hyperkaliämie möglichst nicht sofort absetzen

14.05.2024 Hyperkaliämie Nachrichten

Bei ausgeprägter Nierenfunktionsstörung steigen unter der Einnahme von Renin-Angiotensin-System(RAS)-Hemmstoffen nicht selten die Serumkaliumspiegel. Was in diesem Fall zu tun ist, erklärte Prof. Jürgen Floege beim diesjährigen Allgemeinmedizin-Update-Seminar.

Gestationsdiabetes: In der zweiten Schwangerschaft folgenreicher als in der ersten

13.05.2024 Gestationsdiabetes Nachrichten

Das Risiko, nach einem Gestationsdiabetes einen Typ-2-Diabetes zu entwickeln, hängt nicht nur von der Zahl, sondern auch von der Reihenfolge der betroffenen Schwangerschaften ab.

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

13.05.2024 Pankreaskarzinom Nachrichten

Gerade bei aggressiven Malignomen wie dem duktalen Adenokarzinom des Pankreas könnte Früherkennung die Therapiechancen verbessern. Noch jedoch klafft hier eine Lücke. Ein Studienteam hat einen Weg gesucht, sie zu schließen.

Battle of Experts: Sport vs. Spritze bei Adipositas und Typ-2-Diabetes

11.05.2024 DDG-Jahrestagung 2024 Kongressbericht

Im Battle of Experts traten zwei Experten auf dem Diabeteskongress gegeneinander an: Die eine vertrat die Auffassung „Sport statt Spritze“ bei Adipositas und Typ-2-Diabetes, der andere forderte „Spritze statt Sport!“ Am Ende waren sie sich aber einig: Die Kombination aus beidem erzielt die besten Ergebnisse.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.