Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive pulmonary disease

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

fibroblast growth factor 10

terbutaline

adult

animal experiment

animal model

article

chronic obstructive lung disease

clinical article

controlled study

forced expiratory volume

gene loss

gene mutation

genetic variability

haploinsufficiency

heterozygote

human

inspiratory capacity

lung function

mouse

nonhuman

phenotype

priority journal

sibling

signal transduction

spirometry

total lung capacity

vital capacity

Adolescent

Aged

Analysis of Variance

Animals

Female

Genetic Predisposition to Disease

Humans

Male

Mice

Mice

Transgenic

Middle Aged

Pulmonary Disease

Chronic Obstructive

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)