title: Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Genetic factors influencing lung function may predispose to chronic obstructive pulmonary disease (COPD). The fibroblast growth factor 10 (FGF10) signalling pathway is critical for lung development and lung epithelial renewal. The hypothesis behind this study was that constitutive FGF10 insufficiency may lead to pulmonary disorder. Therefore investigation of the pulmonary functions of patients heterozygous for loss of function mutations in the FGF10 gene was performed.
  
  
  METHODS
  The spirometric measures of lung function from patients and non-carrier siblings were compared and both groups were related to matched reference data for normal human lung function.
  
  
  RESULTS
  The patients show a significant decrease in lung function parameters when compared to control values. The average FEV1/IVC quota (FEV1%) for the patients is 0.65 (80% of predicted) and reversibility test using Terbutalin resulted in a 3.7% increase in FEV1. Patients with FGF10 haploinsufficiency have lung function parameters indicating COPD. A modest response to Terbutalin confirms an irreversible obstructive lung disease.
  
  
  CONCLUSIONS
  These findings support the idea that genetic variants affecting the FGF10 signalling pathway are important determinants of lung function that may ultimately contribute to COPD. Specifically, the results show that FGF10 haploinsufficiency affects lung function measures providing a model for a dosage sensitive effect of FGF10 in the development of COPD.
authors: Department of Immunology, Genetics and Pathology, Science for Life Laboratory and Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors: Joakim
authors: J
authors: Klar
authors: Peter
authors: P
authors: Blomstrand
authors: Charlott
authors: C
authors: Brunmark
authors: Jitendra
authors: J
authors: Badhai
authors: Hanna Falk
authors: HF
authors: Håkansson
authors: Charlotte Sollie
authors: CS
authors: Brange
authors: Birgitta
authors: B
authors: Bergendal
authors: Niklas
authors: N
authors: Dahl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000235:genetics*; D005541:Forced Expiratory Volume / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D057895:Haploinsufficiency; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000503:physiopathology; D013726:Terbutaline / Q000494:pharmacology
chemical_list: C496463:FGF10 protein, human; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D013726:Terbutaline