CHRNA3 and CYP3A5*3 genotype, lung function and chronic obstructive pulmonary disease in the general population.

Objective Genetic variations are most likely an additional risk factor besides tobacco smoking per se for the risk of chronic obstructive pulmonary disease (COPD). In this study, we compared genetic variants influencing the effect of smoking on COPD, that is, the effect of the well-known splicing defect polymorphism, CYP3A5*3 (rs776746), identified before genome-wide association studies, with the genome-wide association studies identified CHRNA3 (rs1051730) polymorphism on the risk of decreased lung function and COPD. Materials and methods In all, 10 605 participants from the general population were genotyped. Information on spirometry, hospital admissions and smoking behaviour was recorded. Endpoints were lung function and COPD. Results For CHRNA3, the percentage of forced expiratory volume in 1 s (FEV1%) predicted was 89.3, 90.6 and 92.4% in homozygous, heterozygous and noncarrier ever-smokers (P-trend Conclusion The CHRNA3 genotype is associated with decreased lung function and risk of COPD among ever-smokers, whereas this was not the case for CYP3A5*3.