PT  - JOURNAL ARTICLE
AU  - Joakim Klar
AU  - Hans Matsson
AU  - Cecilia Söderhäll
AU  - Helena Backman
AU  - Anne Lindberg
AU  - Eva Rönmark
AU  - Bo Lundbäck
AU  - Niklas Dahl
TI  - Candidate gene association study of chronic obstructive pulmonary disorder using a targeted high throughput sequencing approach
DP  - 2012 Sep 01
TA  - European Respiratory Journal
PG  - P3960
VI  - 40
IP  - Suppl 56
4099  - http://erj.ersjournals.com/content/40/Suppl_56/P3960.short
4100  - http://erj.ersjournals.com/content/40/Suppl_56/P3960.full
SO  - Eur Respir J2012 Sep 01; 40
AB  - Background: Genetic studies in humans and in animal models suggest that genes associated with lung developmental processes are also implicated in the development of COPD.Aim: We aim to investigating candidate genes, with emphasis on genes important for lung development, for genetic variants predisposing to the development of chronic obstructive pulmonary disease (COPD) using targeted enrichment in a cohort of COPD patients.Methods: Twelve patients with heterozygous loss of function mutations in a lung developmental gene, the fibroblast growth factor 10 (FGF10), was investigated for pulmonary functions and COPD was classified according to the ATS/ERS 2005 standard. To identify novel variants associated with COPD, we are currently conducting a candidate gene association approach using targeted enrichment (HaloPlex; Halo Genomics) and high throughput sequencing (Illumina) using patients and controls retrieved from the Swedish Obstructive Lung Disease in Norrbotten (OLIN) sample set. This strategy allows for the detection of all genetic variants in the enriched sequence, without the limitations when investigating known variants using SNP arrays.Results: Patients carrying mutations in FGF10 show a significant decrease in lung function parameters consistent with COPD. Based on these results, we are currently investigating in total 200 kb enriched sequence, including 22 genes implicated in lung development and 71 genes or regions previously associated to COPD.Conclusion: These findings support the idea that genetic variants affecting lung developmental genes are important determinants of adult lung function that may ultimately contribute to COPD.