title: Candidate genes for COPD in two large data sets.
abstract: Lack of reproducibility of findings has been a criticism of genetic association studies on complex diseases, such as chronic obstructive pulmonary disease (COPD). We selected 257 polymorphisms of 16 genes with reported or potential relationships to COPD and genotyped these variants in a case-control study that included 953 COPD cases and 956 control subjects. We explored the association of these polymorphisms to three COPD phenotypes: a COPD binary phenotype and two quantitative traits (post-bronchodilator forced expiratory volume in 1 s (FEV₁) % predicted and FEV₁/forced vital capacity (FVC)). The polymorphisms significantly associated to these phenotypes in this first study were tested in a second, family-based study that included 635 pedigrees with 1,910 individuals. Significant associations to the binary COPD phenotype in both populations were seen for STAT1 (rs13010343) and NFKBIB/SIRT2 (rs2241704) (p<0.05). Single-nucleotide polymorphisms rs17467825 and rs1155563 of the GC gene were significantly associated with FEV₁ % predicted and FEV₁/FVC, respectively, in both populations (p<0.05). This study has replicated associations to COPD phenotypes in the STAT1, NFKBIB/SIRT2 and GC genes in two independent populations, the associations of the former two genes representing novel findings.
authors.affiliation: Dept of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway. per.bakke@med.uib.no
authors.forename: P S
authors.initials: PS
authors.lastname: Bakke
authors.forename: G
authors.initials: G
authors.lastname: Zhu
authors.forename: A
authors.initials: A
authors.lastname: Gulsvik
authors.forename: X
authors.initials: X
authors.lastname: Kong
authors.forename: A G N
authors.initials: AG
authors.lastname: Agusti
authors.forename: P M A
authors.initials: PM
authors.lastname: Calverley
authors.forename: C F
authors.initials: CF
authors.lastname: Donner
authors.forename: R D
authors.initials: RD
authors.lastname: Levy
authors.forename: B J
authors.initials: BJ
authors.lastname: Make
authors.forename: P D
authors.initials: PD
authors.lastname: Paré
authors.forename: S I
authors.initials: SI
authors.lastname: Rennard
authors.forename: J
authors.initials: J
authors.lastname: Vestbo
authors.forename: E F M
authors.initials: EF
authors.lastname: Wouters
authors.forename: W
authors.initials: W
authors.lastname: Anderson
authors.forename: D A
authors.initials: DA
authors.lastname: Lomas
authors.forename: E K
authors.initials: EK
authors.lastname: Silverman
authors.forename: S G
authors.initials: SG
authors.lastname: Pillai
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000235:genetics*; D012129:Respiratory Function Tests / Q000706:statistics & numerical data; D050794:STAT1 Transcription Factor / Q000235:genetics*; D056565:Sirtuin 2 / Q000235:genetics*; D012907:Smoking / Q000453:epidemiology; D014809:Vitamin D-Binding Protein / Q000235:genetics*
chemical_list: D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014809:Vitamin D-Binding Protein; C474199:SIRT2 protein, human; D056565:Sirtuin 2