title: Duplicated copy of CHRNA7 increases risk and worsens prognosis of COPD and lung cancer.
abstract: Recent genome-wide association studies implicated that the nicotinic acetylcholine receptors (nAChRs) are common susceptible genes of two contextual diseases: chronic obstructive pulmonary disease (COPD) and lung cancer. We aimed to test whether the copy number variations (CNVs) in nAChRs have hereditary contributions to development of the two diseases. In two, two-stage, case-control studies of southern and eastern Chinese, a common CNV-3956 that duplicates the cholinergic receptor, nicotinic, α7 (CHRNA7) gene was genotyped in a total of 7880 subjects and its biological phenotype was assessed. The ≥4-copy of CNV-3956 increased COPD risk (≥4-copy vs 2/3-copy: OR=1.44, 95% CI=1.23-1.68) and caused poor lung function, and it similarly augmented risk (OR=1.49, 95% CI=1.29-1.73) and worsened prognosis (hazard ratio (HR)=1.25, 95% CI=1.07-1.45) of lung cancer. The ≥4-copy was estimated to account for 1.56% of COPD heritability and 1.87% of lung cancer heritability, respectively. Phenotypic analysis further showed that the ≥4-copy of CNV-3956 improved CHRNA7 expression in vivo and increased the carriers' smoking amount. The CNV-3956 of CHRNA7 contributed to increased risks and poor prognoses of both COPD and lung cancer, and this may be a genetic biomarker of the two diseases.
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: 1] The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, China [2] Colby-Sawyer College, New London, NH, USA.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Lu
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, China.
authors.forename: Fuman
authors.initials: F
authors.lastname: Qiu
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Fang
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Guangzhou Chest Hospital, Guangzhou, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Huang
authors.affiliation: 1] The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, China [2] Dongguan Taiping People Hospital, Dongguan, China.
authors.forename: Chenli
authors.initials: C
authors.lastname: Xie
authors.affiliation: The First Affiliated Hospital, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.
authors.forename: Nanshan
authors.initials: N
authors.lastname: Zhong
authors.affiliation: The First Affiliated Hospital, The State Key Lab of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.
authors.forename: Pixin
authors.initials: P
authors.lastname: Ran
authors.affiliation: Department of Genetics, Medical College of Soochow University, Suzhou, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, China.
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
mesh_terms: D044466:Asian People; D016022:Case-Control Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics*
chemical_list: C579167:Chrna7 protein, human; D064569:alpha7 Nicotinic Acetylcholine Receptor