association of tlr4-t399i polymorphism with chronic obstructive pulmonary disease in smokers协会tlr4-t399i多态性与慢性阻塞性肺疾病的吸烟者.pdfVIP

Hindawi Publishing Corporation Clinical and Developmental Immunology Volume 2009, Article ID 260286, 6 pages doi:10.1155/2009/260286 Research Article Association of TLR4-T399I Polymorphism with Chronic Obstructive Pulmonary Disease in Smokers Matthaios Speletas,1 Vassiliki Merentiti,1 Konstantinos Kostikas,2 Kyriaki Liadaki,1 Markos Minas,2 Konstantinos Gourgoulianis,2 and Anastasios E. Germenis1 1 Department of Immunology and Histocompatibility, University of Thessaly Medical School, 41110 Larissa, Greece 2 Respiratory Medicine Department, University of Thessaly Medical School, 41110 Larissa, Greece Correspondence should be addressed to Matthaios Speletas, maspel@med.uth.gr Received 5 August 2009; Revised 9 December 2009; Accepted 30 December 2009 Recommended by Nima Rezaei Tobacco smoking has been considered the most important risk factor for chronic obstructive pulmonary disease (COPD) development. However, not all smokers develop COPD and other environmental and genetic susceptibility factors underlie disease pathogenesis. Recent studies have indicated that the impairment of TLR signaling might play a crucial role in the development of emphysema. For this purpose we investigated the prevalence and any possible associations of common TLR polymorphisms (TLR2-R753Q, TLR4-D299G, and TLR4-T399I) in a group of 240 heavy smokers ( 20 pack years), without overt atherosclerosis disease, of whom 136 had developed COPD and 104 had not. The presence of TLR4-T399I polymorphism was associated with a 2.4-fold increased risk for COPD development (P = .044), but not with disease stage or frequency of exacerbations. Considering that infections contribute to COPD and emphysema pathogenesis, our findings possibly indicate that dysfunctional