Association of TLR4-T399I Polymorphism with Chronic Obstructive Pulmonary Disease in Smokers

Overview

Journal Clin Dev Immunol

Specialty Allergy & Immunology

Date 2010 Feb 20

PMID 20169003

Citations 26

Authors

Matthaios Speletas

Vassiliki Merentiti

Konstantinos Kostikas

Kyriaki Liadaki

Markos Minas

Konstantinos Gourgoulianis

Anastasios E Germenis

Affiliations

Soon will be listed here.

Abstract

Tobacco smoking has been considered the most important risk factor for chronic obstructive pulmonary disease (COPD) development. However, not all smokers develop COPD and other environmental and genetic susceptibility factors underlie disease pathogenesis. Recent studies have indicated that the impairment of TLR signaling might play a crucial role in the development of emphysema. For this purpose we investigated the prevalence and any possible associations of common TLR polymorphisms (TLR2-R753Q, TLR4-D299G, and TLR4-T399I) in a group of 240 heavy smokers (>20 pack years), without overt atherosclerosis disease, of whom 136 had developed COPD and 104 had not. The presence of TLR4-T399I polymorphism was associated with a 2.4-fold increased risk for COPD development (P = .044), but not with disease stage or frequency of exacerbations. Considering that infections contribute to COPD and emphysema pathogenesis, our findings possibly indicate that dysfunctional polymorphisms of innate immune genes can affect the development of COPD in smokers. Although this finding warrants further investigation, it highlights the importance of impaired innate immunity towards COPD development.

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References

Schroder N, Hermann C, Hamann L, Gobel U, Hartung T, Schumann R . High frequency of polymorphism Arg753Gln of the Toll-like receptor-2 gene detected by a novel allele-specific PCR. J Mol Med (Berl). 2003; 81(6):368-72. DOI: 10.1007/s00109-003-0443-x. View

Monso E, Ruiz J, Rosell A, Manterola J, Fiz J, Morera J . Bacterial infection in chronic obstructive pulmonary disease. A study of stable and exacerbated outpatients using the protected specimen brush. Am J Respir Crit Care Med. 1995; 152(4 Pt 1):1316-20. DOI: 10.1164/ajrccm.152.4.7551388. View

Zintzaras E, Lau J . Trends in meta-analysis of genetic association studies. J Hum Genet. 2007; 53(1):1-9. DOI: 10.1007/s10038-007-0223-5. View

Speletas M, Vyzantiadis T, Kalala F, Plastiras D, Kokoviadou K, Antoniadis A . Pneumonia caused by Candida krusei and Candida glabrata in a patient with chronic myeloid leukemia receiving imatinib mesylate treatment. Med Mycol. 2007; 46(3):259-63. DOI: 10.1080/13693780701558969. View

Ioannidis J, Ntzani E, Trikalinos T, Contopoulos-Ioannidis D . Replication validity of genetic association studies. Nat Genet. 2001; 29(3):306-9. DOI: 10.1038/ng749. View

Johnson G, Brunn G, Kodaira Y, Platt J . Receptor-mediated monitoring of tissue well-being via detection of soluble heparan sulfate by Toll-like receptor 4. J Immunol. 2002; 168(10):5233-9. DOI: 10.4049/jimmunol.168.10.5233. View

Kitsios G, Zintzaras E . Genome-wide association studies: hypothesis-"free" or "engaged"?. Transl Res. 2009; 154(4):161-4. PMC: 2971665. DOI: 10.1016/j.trsl.2009.07.001. View

Sabroe I, Whyte M, Wilson A, Dower S, Hubbard R, Hall I . Toll-like receptor (TLR) 4 polymorphisms and COPD. Thorax. 2003; 59(1):81. PMC: 1758836. View

Rohde G, Klein W, Arinir U, Hagedorn M, Duerig N, Bauer T . Association of the ASP299GLY TLR4 polymorphism with COPD. Respir Med. 2005; 100(5):892-6. DOI: 10.1016/j.rmed.2005.08.018. View

10.

Curtis J, Freeman C, Hogg J . The immunopathogenesis of chronic obstructive pulmonary disease: insights from recent research. Proc Am Thorac Soc. 2007; 4(7):512-21. PMC: 2365762. DOI: 10.1513/pats.200701-002FM. View

11.

Maes T, Bracke K, Vermaelen K, Demedts I, Joos G, Pauwels R . Murine TLR4 is implicated in cigarette smoke-induced pulmonary inflammation. Int Arch Allergy Immunol. 2006; 141(4):354-68. DOI: 10.1159/000095462. View

12.

Arbour N, Lorenz E, Schutte B, Zabner J, Kline J, Jones M . TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet. 2000; 25(2):187-91. DOI: 10.1038/76048. View

13.

Kiechl S, Lorenz E, Reindl M, Wiedermann C, Oberhollenzer F, Bonora E . Toll-like receptor 4 polymorphisms and atherogenesis. N Engl J Med. 2002; 347(3):185-92. DOI: 10.1056/NEJMoa012673. View

14.

Taraseviciene-Stewart L, Voelkel N . Molecular pathogenesis of emphysema. J Clin Invest. 2008; 118(2):394-402. PMC: 2214683. DOI: 10.1172/JCI31811. View

15.

Mannino D . COPD: epidemiology, prevalence, morbidity and mortality, and disease heterogeneity. Chest. 2002; 121(5 Suppl):121S-126S. DOI: 10.1378/chest.121.5_suppl.121s. View

16.

Ogus A, Yoldas B, Ozdemir T, Uguz A, Olcen S, Keser I . The Arg753GLn polymorphism of the human toll-like receptor 2 gene in tuberculosis disease. Eur Respir J. 2004; 23(2):219-23. DOI: 10.1183/09031936.03.00061703. View

17.

Rabe K, Hurd S, Anzueto A, Barnes P, Buist S, Calverley P . Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007; 176(6):532-55. DOI: 10.1164/rccm.200703-456SO. View

18.

Torok H, Glas J, Tonenchi L, Mussack T, Folwaczny C . Polymorphisms of the lipopolysaccharide-signaling complex in inflammatory bowel disease: association of a mutation in the Toll-like receptor 4 gene with ulcerative colitis. Clin Immunol. 2004; 112(1):85-91. DOI: 10.1016/j.clim.2004.03.002. View

19.

Hogg J, Chu F, Utokaparch S, Woods R, Elliott W, Buzatu L . The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004; 350(26):2645-53. DOI: 10.1056/NEJMoa032158. View

20.

Barker D, Godfrey K, Fall C, Osmond C, WINTER P, Shaheen S . Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease. BMJ. 1991; 303(6804):671-5. PMC: 1670943. DOI: 10.1136/bmj.303.6804.671. View