Linking gene polymorphisms with COPD onset and pathology

PhD ceremony: Ms. S.E. Budulac, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Linking gene polymorphisms with COPD onset and pathology

Promotor(s): prof. H.M. Boezen, prof. D.S. Postma, prof. W. Timens

Faculty: Medical Sciences

Chronic Obstructive Pulmonary Disease (COPD) is clinically characterized by irreversible airway obstruction and an accelerated decline in lung function generally with or without respiratory symptoms like cough, phlegm and dyspnea. Cigarette smoking is the most important risk factor for the development of COPD. The low percentage of variance in pulmonary function that is explained by smoking suggests genetic differences in susceptibility to its effects. The mechanisms contributing to structural and functional changes in the lungs of COPD patients are protease-antiprotease and oxidant-antioxidant imbalance, and increased inflammation. We investigated several genetic variants in genes involved in the above mentioned mechanisms in relation to the level and decline of lung function in the general population (Doetinchem and Vlagtwedde-Vlaardingen study populations) and to inflammatory markers in bronchial biopsies and induced sputum in patients with established COPD (GLUCOLD study). We investigated the genetic variations in multidrug resistance-associated protein 1 (MRP1), Toll-like receptors (TLR2 and TLR4), a developmental geneHedgehog-interacting protein (HHIP), and n icotinic acetylcholine receptor (nAChR) a controversial gene with respect to its association with COPD and smoking addiction.