Association of Lung Function Genes with Chronic Obstructive Pulmonary Disease

• Published in: Lung 2014-08, Vol.192 (4), p.473-480
• Main Authors: Kim, Woo Jin, Lim, Myoung Nam, Hong, Yoonki, Silverman, Edwin K., Lee, Ji-Hyun, Jung, Bock Hyun, Ra, Seung Won, Choi, Hye Sook, Jung, Young Ju, Park, Yong Bum, Park, Myung Jae, Lee, Sei Won, Lee, Jae Seung, Oh, Yeon-Mok, Lee, Sang Do
• Format: Article
• Language: English
• Subjects: Age Factors; Aged; Care and treatment; Carrier Proteins - genetics; Case-Control Studies; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Complications and side effects; Development and progression; Female; Gene expression; Gene Frequency; Genetic aspects; Genetic Association Studies; Genetic Predisposition to Disease; GTPase-Activating Proteins - genetics; Health aspects; Humans; Lung - physiopathology; Lung diseases, Obstructive; Male; Medicine; Medicine & Public Health; Middle Aged; Outpatient Clinics, Hospital; Patient outcomes; Phenotype; Pneumology/Respiratory System; Polymorphism, Single Nucleotide; Predictive Value of Tests; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - physiopathology; Republic of Korea; Risk Factors; Sex Factors; Smoking; Smoking - adverse effects; Spirometry
• ISSN: 0341-2040; 1432-1750
• DOI: 10.1007/s00408-014-9579-4

Background Spirometric measurements of pulmonary function are important in diagnosing and determining the severity of chronic obstructive pulmonary disease (COPD). We performed this study to determine whether candidate genes identified in genome-wide association studies of spirometric measurements were associated with COPD and if they interacted with smoking intensity. Methods The current analysis included 1,000 COPD subjects and 1,000 controls recruited from 24 hospital-based pulmonary clinics. Thirteen SNPs, chosen based on genome-wide association studies of spirometric measurements in the Korean population cohorts, were genotyped. Genetic association tests were performed, adjusting for age, sex, and smoking intensity, using models including a SNP-by-smoking interaction term. Results PID1 and FAM13A were significantly associated with COPD susceptibility. There were also significant interactions between SNPs in ACN9 and FAM13A and smoking pack-years, and an association of ACN9 with COPD in the lowest smoking tertile. The risk allele of FAM13A was associated with increased expression of FAM13A in the lung. Conclusions We have validated associations of FAM13A and PID1 with COPD. ACN9 showed significant interaction with smoking and is a potential candidate gene for COPD. Significant associations of genetic variants of FAM13A with gene expression levels suggest that the associated loci may act as genetic regulatory elements for FAM13A gene expression.