Association of the ASP299GLY TLR 4 polymorphism with COPD

• Published in: Respiratory medicine Vol. 100; no. 5; p. 892
• Main Authors: Rohde, Gernot, Klein, Wolfram, Arinir, Umut, Hagedorn, Michaela, Duerig, Natascha, T. Bauer, Torsten, Gillissen, Adrian, Schultze-Werninghaus, Gerhard, T. Epplen, Jörg
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Limited 01.05.2006
• Subjects: Airway management; Confidence intervals; Cytokines; Genes; Genotype & phenotype; Health risk assessment; Lungs; Mutation; Pathogenesis; Signal transduction; Streptococcus infections
• ISSN: 0954-6111; 1532-3064
• DOI: 10.1016/j.rmed.2005.08.018

Bacterial infection and colonization plays an important role in COPD. The inflammatory response to these bacteria is mediated by Toll-like receptors. The Asp299Gly polymorphism of the Toll-like receptor-4 (TLR 4) has been shown to be associated with decreased lipopolysaccharide (LPS) signal transduction resulting in impaired antimicrobial defense. Because altered TLR 4 signalling may facilitate bacterial infection, we clinically phenotyped and genotyped 152 patients with COPD (including 24 non-smokers), and 444 healthy controls for the presence of the Asp299Gly polymorphism. Frequencies of the TLR 4 Gly allele (4% vs. 8% in controls, odds ratio (OR) 2.24 (95% confidence interval (95%CI) 1.17-4.3)) as well as TLR 4 Gly genotype (6% vs. 13% in controls, OR 2.39 (95%CI 1.20-4.79)) were significantly decreased among the patients with COPD. The TLR 4 Gly allele was not detected at all in a subgroup of non-smoking patients (). We conclude that the frequency of the Asp299Gly polymorphism is decreased in COPD patients. Unaltered LPS signal transduction by TLR 4 may be important for the development of COPD.