Transforming growth factor-beta1 polymorphisms, airway responsiveness and lung function decline in smokers

Respir Med. 2007 May;101(5):938-43. doi: 10.1016/j.rmed.2006.09.008. Epub 2006 Oct 27.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchoconstrictor Agents
  • Case-Control Studies
  • Disease Progression
  • Female
  • Forced Expiratory Volume*
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Male
  • Methacholine Chloride
  • Middle Aged
  • Polymorphism, Genetic*
  • Respiratory Hypersensitivity / genetics*
  • Respiratory Hypersensitivity / physiopathology
  • Smoking / genetics*
  • Smoking / physiopathology
  • Transforming Growth Factor beta1 / genetics*


  • Bronchoconstrictor Agents
  • Transforming Growth Factor beta1
  • Methacholine Chloride