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Functional polymorphisms of CHRNA3 predict risks of chronic obstructive pulmonary disease and lung cancer in Chinese.

dc.contributor.author Yang, Lei
dc.contributor.author Qiu, Fuman
dc.contributor.author Lu, Xiaoxiao
dc.contributor.author Huang, Dongsheng
dc.contributor.author Ma, Guanpei
dc.contributor.author Guo, Yuan
dc.contributor.author Hu, Min
dc.contributor.author Zhou, Yumin
dc.contributor.author Pan, Mingan
dc.contributor.author Tan, Yigang
dc.contributor.author Zhong, Haibo
dc.contributor.author Ji, Weidong
dc.contributor.author Wei, Qingyi
dc.contributor.author Ran, Pixin
dc.contributor.author Zhong, Nanshan
dc.contributor.author Zhou, Yifeng
dc.contributor.author Lu, Jiachun
dc.date.accessioned 2019-02-01T15:11:49Z
dc.date.available 2019-02-01T15:11:49Z
dc.date.issued 2012-01
dc.identifier PONE-D-12-11340
dc.identifier.issn 1932-6203
dc.identifier.issn 1932-6203
dc.identifier.uri https://hdl.handle.net/10161/17984
dc.description.abstract Recently, several genome-wide association studies (GWAS) have identified many susceptible single nucleotide polymorphisms (SNPs) for chronic obstructive pulmonary disease (COPD) and lung cancer which are two closely related diseases. Among those SNPs, some of them are shared by both the diseases, reflecting there is possible genetic similarity between the diseases. Here we tested the hypothesis that whether those shared SNPs are common predictor for risks or prognosis of COPD and lung cancer. Two SNPs (rs6495309 and rs1051730) located in nicotinic acetylcholine receptor alpha 3 (CHRNA3) gene were genotyped in 1511 patients with COPD, 1559 lung cancer cases and 1677 controls in southern and eastern Chinese populations. We found that the rs6495309CC and rs6495309CT/CC variant genotypes were associated with increased risks of COPD (OR = 1.32, 95% C.I. = 1.14-1.54) and lung cancer (OR = 1.57; 95% CI = 1.31-1.87), respectively. The rs6495309CC genotype contributed to more rapid decline of annual Forced expiratory volume in one second (FEV1) in both COPD cases and controls (P<0.05), and it was associated with advanced stages of COPD (P = 0.033); the rs6495309CT/CC genotypes conferred a poor survival for lung cancer (HR = 1.41, 95%CI = 1.13-1.75). The luciferase assays further showed that nicotine and other tobacco chemicals had diverse effects on the luciferase activity of the rs6495309C or T alleles. However, none of these effects were found for another SNP, rs1051730G>A. The data show a statistical association and suggest biological plausibility that the rs6495309T>C polymorphism contributed to increased risks and poor prognosis of both COPD and lung cancer.
dc.language eng
dc.publisher Public Library of Science (PLoS)
dc.relation.ispartof PloS one
dc.relation.isversionof 10.1371/journal.pone.0046071
dc.subject Humans
dc.subject Lung Neoplasms
dc.subject Pulmonary Disease, Chronic Obstructive
dc.subject Genetic Predisposition to Disease
dc.subject Receptors, Nicotinic
dc.subject Respiratory Function Tests
dc.subject Prognosis
dc.subject Linear Models
dc.subject Risk Factors
dc.subject Case-Control Studies
dc.subject Gene Frequency
dc.subject Genotype
dc.subject Haplotypes
dc.subject Polymorphism, Single Nucleotide
dc.subject Alleles
dc.subject Middle Aged
dc.subject Asian Continental Ancestry Group
dc.subject China
dc.subject Female
dc.subject Male
dc.subject Genome-Wide Association Study
dc.subject Kaplan-Meier Estimate
dc.title Functional polymorphisms of CHRNA3 predict risks of chronic obstructive pulmonary disease and lung cancer in Chinese.
dc.type Journal article
duke.contributor.id Wei, Qingyi|0632334
dc.date.updated 2019-02-01T15:11:48Z
pubs.begin-page e46071
pubs.issue 10
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Population Health Sciences
pubs.organisational-group Basic Science Departments
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group Medicine
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
pubs.volume 7
duke.contributor.orcid Wei, Qingyi|0000-0002-3845-9445


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