Association of the ASP299GLY TLR4 polymorphism with COPD.

Summary 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 ( n = 24 ). 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.