Toll-Like Receptor (<em>TLR2</em> and <em>TLR4</em>) Polymorphisms and Chronic Obstructive Pulmonary Disease

<div><p>Toll-like receptors (TLRs) participate in the defence against bacterial infections that are common in patients with Chronic Obstructive Pulmonary Disease (COPD). We studied all tagging SNPs in <em>TLR2</em> and <em>TLR4</em> and their associations with the level and change over time of both FEV₁ and sputum inflammatory cells in moderate-to-severe COPD. Nine <em>TLR2</em> SNPs and 17 <em>TLR4</em> SNPs were genotyped in 110 COPD patients. Associations of SNPs with lung function and inflammatory cells in induced sputum were analyzed cross-sectionally with linear regression and longitudinally with linear mixed-effect models. Two SNPs in <em>TLR2</em> (rs1898830 and rs11938228) were associated with a lower level of FEV₁ and accelerated decline of FEV₁ and higher numbers of sputum inflammatory cells. None of the <em>TLR4</em> SNPs was associated with FEV₁ level. Eleven out of 17 SNPs were associated with FEV₁ decline, including rs12377632 and rs10759931, which were additionally associated with higher numbers of sputum inflammatory cells at baseline and with increase over time. This is the first longitudinal study showing that tagging SNPs in <em>TLR2</em> and <em>TLR4</em> are associated with the level and decline of lung function as well as with inflammatory cell numbers in induced sputum in COPD patients, suggesting a role in the severity and progression of COPD.</p>