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-β1 (TGF-β1), 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-β1 gene would be associated with an accelerated rate of decline of forced expiratory volume in 1 s (FEV1). Three polymorphisms, -509 (C→T), +869 (T→C) and +915 (G→C), located in TGF-β1 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-β1 polymorphisms and the rate of decline of FEV1, 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-β1 gene contributes to airway hyperresponsiveness, but not to rapid decline of lung function.
Bibliographical noteFunding Information:
The authors gratefully acknowledge the NHLBI for the recruitment and characterization of this study. The authors wish to thank Melissa Skeans for her insightful review of the manuscript. AJS is the recipient of a Canada Research Chair in genetics and a Michael Smith Foundation for Health Research Scholar Award.
- Airway hyperresponsiveness
- Forced expiratory volume
- Genetic predisposition to disease