title: CHRNA5/CHRNA3 Locus Associates with Increased Mortality among Smokers.
abstract: Polymorphisms in the nicotinic acetylcholine receptor gene (CHRNA5/CHRNA3 locus) have been associated with several smoking related traits such as nicotine dependence, cigarette consumption, smoking cessation, lung cancer, and COPD. The aim of this candidate gene study was to study the locus among the Finnish COPD patients and long-term smokers with regard to COPD risk, smoking behavior, cancer, and all-cause mortality. Genotyping of rs1051730, the locus tagging SNP was done in two longitudinal cohorts: Finnish COPD patients (N = 575, 74% men) and long-term smokers, all men (N = 1911). Finnish population sample (N = 1730) was used as controls. The analyses were done using logistic and Cox regression. The main findings were that the minor allele increased the risk of COPD when compared to the Finnish population at large (OR = 1.4, 95% CI 1.2-1.7, p = 3.2 × 10-5). Homozygosity for the risk allele was associated in both cohorts with all-cause mortality (crude HR 2.2, 95% CI 1.2-3.8 and 1.3, 95% CI 1.1-1.5, respectively), with any type of cancer (crude OR 2.3, 95% CI 1.0-5.1) among the COPD patients and with the number of pack-years (crude OR 1.4, 95% CI 1.1-1.9) among the male smokers. CHRNA5/CHRNA3 locus tagged by rs1051730, which has been previously associated with several smoking related diseases was now shown to be associated also with increased all-cause mortality among long-term smokers with or without clinical COPD further emphasizing the clinical importance of the finding.
authors.affiliation: a Department of Pulmonary Diseases and Clinical Allergology , University of Turku and Turku University Hospital, Turku, Finland.|b Department of Pulmonary Diseases and Clinical Allergology , Helsinki University Central Hospital , Helsinki , Finland.
authors.forename: Henna
authors.initials: H
authors.lastname: Kupiainen
authors.affiliation: b Department of Pulmonary Diseases and Clinical Allergology , Helsinki University Central Hospital , Helsinki , Finland.|c Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Kuokkanen
authors.affiliation: c Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Kontto
authors.affiliation: c Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.affiliation: c Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: b Department of Pulmonary Diseases and Clinical Allergology , Helsinki University Central Hospital , Helsinki , Finland.
authors.forename: Ari
authors.initials: A
authors.lastname: Lindqvist
authors.affiliation: a Department of Pulmonary Diseases and Clinical Allergology , University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Maritta
authors.initials: M
authors.lastname: Kilpeläinen
authors.affiliation: a Department of Pulmonary Diseases and Clinical Allergology , University of Turku and Turku University Hospital, Turku, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Laitinen
mesh_terms: D000368:Aged; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009369:Neoplasms / Q000235:genetics / Q000401:mortality; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000401:mortality; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000235:genetics* / Q000401:mortality
chemical_list: D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human
keywords: COPD; mortality; single nucleotide polymorphism; smoking