Department of Immunology, Genetics and Pathology, Science for Life Laboratory and Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
J Med Genet. 2011 Oct;48(10):705-9. doi: 10.1136/jmedgenet-2011-100166. Epub 2011 Jul 8.
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.
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.
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.
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.
影响肺功能的遗传因素可能使慢性阻塞性肺疾病（COPD）易于发生。成纤维细胞生长因子 10（FGF10）信号通路对肺发育和肺上皮更新至关重要。本研究的假设是，组成型 FGF10 不足可能导致肺部疾病。因此，对 FGF10 基因功能丧失突变的杂合子患者的肺功能进行了研究。
比较了患者和非携带者兄弟姐妹的肺功能肺活量测量值，并将两组与正常人体肺功能的匹配参考数据进行了比较。
与对照值相比，患者的肺功能参数明显下降。患者的平均 FEV1/IVC 比值（FEV1%）为 0.65（预测值的 80%），特布他林的可逆性试验导致 FEV1 增加 3.7%。FGF10 部分不足的患者的肺功能参数表明存在 COPD。特布他林的适度反应证实了不可逆的阻塞性肺病。
这些发现支持这样一种观点，即影响 FGF10 信号通路的遗传变异是肺功能的重要决定因素，最终可能导致 COPD。具体而言，结果表明，FGF10 部分不足会影响肺功能测量值，为 FGF10 在 COPD 发展中的剂量敏感效应提供了模型。
