The Asp299Gly Polymorphism of the Toll-Like Receptor-4 gene is associated with reduced risk for COPD

The course of chronic obstructive pulmonary disease (COPD) is characterized by frequent exacerbations. The cause is often infection with Gram positive and Gram negative bacteria. Moreover a chronic bacterial infection in the bronchial tree is prevalent in many COPD patients. The Asp299Gly Polymorphism of the Toll-Like Receptor-4 (TLR4) has been shown to be associated with decreased lipopolysaccharide (LPS) signal transduction. Therefore, we genotyped 153 patients with COPD (including 25 non-smokers), and 463 healthy controls. Frequencies of the TLR4 Gly allele as well as TLR4 Gly genotype were significantly decreased among the patients with COPD (p=0.021, p=0.020). Frequencies were even more decreased among the non-smoking patients. We conclude that altered expression of TLR4 appears to be involved in the genetic predisposition to COPD.