Association of the ASP299GLY TLR4 polymorphism with COPD.
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 (TLR4) has been shown to be associated with decreased lipopolysaccharide (LPS) signal transduction resulting in impaired antimicrobial defense. Because altered TLR4 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 TLR4 Gly allele (4% vs. 8% in controls, odds ratio (OR) 2.24 (95% confidence interval (95%CI) 1.17-4.3)) as well as TLR4 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 TLR4 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 TLR4 may be important for the development of COPD.
Rohde
Gernot
G
Department of Internal Medicine III, Pneumology, Division of Pneumology, Allergology and Sleep Medicine, University Hospital Bergmannsheil, D-44789 Bochum, Germany. gernot.rohde@ruhr-uni-bochum.de
Klein
Wolfram
W
Arinir
Umut
U
Hagedorn
Michaela
M
Duerig
Natascha
N
T Bauer
Torsten
T
Gillissen
Adrian
A
Schultze-Werninghaus
Gerhard
G
T Epplen
Jörg
J
D000368:Aged; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics*
C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4