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Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive pulmonary disease
  1. Joakim Klar1,
  2. Peter Blomstrand2,
  3. Charlott Brunmark3,
  4. Jitendra Badhai1,
  5. Hanna Falk Håkansson3,
  6. Charlotte Sollie Brange3,
  7. Birgitta Bergendal4,
  8. Niklas Dahl1
  1. 1Department of Immunology, Genetics and Pathology, Science for Life Laboratory and Rudbeck Laboratory, Uppsala University, Uppsala, Sweden
  2. 2Department of Clinical Physiology, Ryhov County Hospital, Jönköping, Sweden
  3. 3AstraZeneca R&D, Lund, Sweden
  4. 4National Oral Disability Centre, The Institute for Postgraduate Dental Education, Jönköping, Sweden
  1. Correspondence to Niklas Dahl, Department of Immunology, Genetics and Pathology, Science for Life Laboratory and Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; niklas.dahl{at}


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.

Conclusion 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.

  • Genetics
  • academic medicine
  • asthma
  • cardiovascular medicine
  • respiratory medicine
  • diagnostics
  • immunology (including allergy)
  • other endocrinology
  • drugs: endocrine system
  • molecular genetics
  • metabolic disorders
  • nutrition and metabolism
  • pituitary disorders
  • thyroid disease
  • diabetes
  • adrenal disorders
  • genetic epidemiology
  • obesity
  • metabolic disorders
  • genetics
  • chronic obstructive pulmonary disease (COPD)

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  • Funding This work was supported by the Swedish Research Council, Uppsala University, Uppsala University Hospital, the Swedish Society for Medical Research, and Futurum academy of science and healthcare, Jönköping County Council.

  • Competing interests None.

  • Ethics approval The human studies were approved by the local ethics committee in Jönköping, Sweden, and with the informed consent of the patients. The animal studies were approved by the local ethics committee in Uppsala, Sweden, and performed according to governmental guidelines.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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