title: Transforming growth factor-beta1 polymorphisms, airway responsiveness and lung function decline in smokers.
abstract: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the airways, parenchyma and vessels, which can cause a structural remodeling with increased fibrosis that narrows and fixes the airway lumen. Transforming growth factor-beta1 (TGF-beta1), a multifunctional growth factor, was reported to be increased in the airways of COPD patients. In this study, we hypothesized that polymorphisms in the TGF-beta1 gene would be associated with an accelerated rate of decline of forced expiratory volume in 1s (FEV(1)). Three polymorphisms, -509 (C-->T), +869 (T-->C) and +915 (G-->C), located in TGF-beta1 gene were genotyped. We determined the prevalence of these polymorphisms in 590 continuing smokers who had the fastest (n=283) and slowest (n=307) rate of decline of lung function from the NHLBI Lung Health Study. There was no association between these TGF-beta1 polymorphisms and the rate of decline of FEV(1), but in a post-hoc analysis the genotype distribution at +869 was significantly different between high and low responders to methacholine (P=0.04). These data suggest that the T-C polymorphism at position +869 in the TGF-beta1 gene contributes to airway hyperresponsiveness, but not to rapid decline of lung function.
authors.affiliation: James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St. Paul's Hospital, Room 166, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6.
authors.forename: Emiko
authors.initials: E
authors.lastname: Ogawa
authors.forename: Jian
authors.initials: J
authors.lastname: Ruan
authors.forename: John E
authors.initials: JE
authors.lastname: Connett
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Anthonisen
authors.forename: Peter D
authors.initials: PD
authors.lastname: Paré
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sandford
mesh_terms: D016085:Bronchoconstrictor Agents; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012130:Respiratory Hypersensitivity / Q000235:genetics* / Q000503:physiopathology; D012907:Smoking / Q000235:genetics* / Q000503:physiopathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D016085:Bronchoconstrictor Agents; D053773:Transforming Growth Factor beta1; D016210:Methacholine Chloride