title: CHRNA3/5, IREB2, and ADCY2 are associated with severe chronic obstructive pulmonary disease in Poland.
abstract: We examined the association between single-nucleotide polymorphisms (SNPs) previously associated with chronic obstructive pulmonary disease (COPD) and/or lung function with COPD and COPD-related phenotypes in a novel cohort of patients with severe to very severe COPD. We examined 315 cases of COPD and 330 Caucasian control smokers from Poland. We included three SNPs previously associated with COPD: rs7671167 (FAM13A), rs13180 (IREB2), and rs8034191 (CHRNA 3/5), and four SNPs associated with lung function in a genome-wide association study of general population samples: rs2070600 (AGER), rs11134242 (ADCY2), rs4316710 (THSD4), and rs17096090 (INTS12). We tested for associations with severe COPD and COPD-related phenotypes, including lung function, smoking behavior, and body mass index. Subjects with COPD were older (average age 62 versus 58 years, P < 0.01), with more pack-years of smoking (45 versus 33 pack-years, P < 0.01). CHRNA3/5 (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.5-2.4; P = 7.4 × 10(-7)), IREB2 (OR, 0.69; 95% CI, 0.5-0.9; P = 3.4 × 10(-3)), and ADCY2 (OR, 1.35; 95% CI, 1.1-1.7; P = 0.01) demonstrated significant associations with COPD. FAM13A (OR, 0.8; 95% CI, 0.7-1.0; P = 0.11) approached statistical significance. FAM13A and ADCY2 also demonstrated a significant association with lung function. Thus, in severe to very severe COPD, we demonstrate a replication of association between two SNPs previously associated with COPD (CHRNA3/5 and IREB2), as well as an association with COPD of one locus initially associated with lung function (ADCY2).
authors.affiliation: Channing Laboratory, Brigham and Women's Hospital, Boston, MA 02115, USA. remeh@channing.harvard.edu
authors.forename: Megan
authors.initials: M
authors.lastname: Hardin
authors.forename: Jan
authors.initials: J
authors.lastname: Zielinski
authors.forename: Emily S
authors.initials: ES
authors.lastname: Wan
authors.forename: Craig P
authors.initials: CP
authors.lastname: Hersh
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Castaldi
authors.forename: Eric
authors.initials: E
authors.lastname: Schwinder
authors.forename: Iwona
authors.initials: I
authors.lastname: Hawrylkiewicz
authors.forename: Pawel
authors.initials: P
authors.lastname: Sliwinski
authors.forename: Michael H
authors.initials: MH
authors.lastname: Cho
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D035942:Iron Regulatory Protein 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: D000262:Adenylyl Cyclases; D035942:Iron Regulatory Protein 2; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human; C100622:adenylyl cyclase 2