title: Association of lung function genes with chronic obstructive pulmonary disease.
abstract: 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.
authors.affiliation: Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, South Korea.
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Kim
authors.forename: Myoung Nam
authors.initials: MN
authors.lastname: Lim
authors.forename: Yoonki
authors.initials: Y
authors.lastname: Hong
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Bock Hyun
authors.initials: BH
authors.lastname: Jung
authors.forename: Seung Won
authors.initials: SW
authors.lastname: Ra
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Choi
authors.forename: Young Ju
authors.initials: YJ
authors.lastname: Jung
authors.forename: Yong Bum
authors.initials: YB
authors.lastname: Park
authors.forename: Myung Jae
authors.initials: MJ
authors.lastname: Park
authors.forename: Sei Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Lee
authors.forename: Yeon-Mok
authors.initials: YM
authors.lastname: Oh
authors.forename: Sang Do
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000367:Age Factors; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010044:Outpatient Clinics, Hospital; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D056910:Republic of Korea; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D013147:Spirometry
chemical_list: D002352:Carrier Proteins; C570078:FAM13A protein, human; D020690:GTPase-Activating Proteins; C514653:PID1 protein, human
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