title: The Functional Copy Number Variation-67048 in WWOX Contributes to Increased Risk of COPD in Southern and Eastern Chinese.
abstract: Recent studies have recognized the genetic variants in the WW domain-containing oxidoreductase (WWOX) gene as genetic determinants of lung function, reflecting that the WWOX gene may be a susceptible factor of chronic obstructive pulmonary disease (COPD), which characters as poor lung function. We have previously showed that the copy number variation-67048 (CNV-67048) of WWOX was associated with lung cancer risk. Here, we hypothesized that the CNV-67048 affects COPD susceptibility. Based on a two-stage case-control study with a total of 1791 COPD patients and 1940 controls of southern and eastern Chinese, we found that the loss genotypes (0-copy and 1-copy) of CNV-67048 harbored a significantly increased risk of COPD, with an odds ratio (OR) as 1.29 (1.11-1.49) when compared with the common 2-copy genotype. The pre-forced expiratory volume in one second (pre-FEV1) to pre-forced vital capacity (pre-FVC) of carriers with loss genotypes (0.729 ± 0.130) was significantly lower than carriers with 2-copy genotype (0.747 ± 0.124; p = 7.93 × 10(-5)). However, no significant difference was observed on pre-FEV1, pre-FVC and the annual decline of pre-FEV1 between the loss genotypes and 2-copy genotype carriers. Our data suggest that the loss genotypes of CNV-67048 in WWOX predispose their carriers to COPD, which might be a genetic biomarker to predict risk of COPD in Chinese.
authors.affiliation: a The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis , Guangzhou Medical University , Guangzhou , China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: a The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis , Guangzhou Medical University , Guangzhou , China.
authors.forename: Fuman
authors.initials: F
authors.lastname: Qiu
authors.affiliation: a The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis , Guangzhou Medical University , Guangzhou , China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Fang
authors.affiliation: a The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis , Guangzhou Medical University , Guangzhou , China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Zhang
authors.affiliation: a The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis , Guangzhou Medical University , Guangzhou , China.|b Dongguan Taiping People Hospital , Dongguan , China.
authors.forename: Chenli
authors.initials: C
authors.lastname: Xie
authors.affiliation: a The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis , Guangzhou Medical University , Guangzhou , China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Lu
authors.affiliation: c Department of Respiratory Medicine , Guangzhou Chest Hospital , Guangzhou , China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Huang
authors.affiliation: d The Third Affiliated Hospital of Guangzhou Medical University , Guangzhou , China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: e Department of Respiratory Medicine , the third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
authors.forename: Mingan
authors.initials: M
authors.lastname: Pan
authors.affiliation: f Department of Respiratory Medicine , Guangzhou Red Cross Hospital , Guangzhou , China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: g Department of Genetics , Medical College of Soochow University , Suzhou , China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: a The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis , Guangzhou Medical University , Guangzhou , China.
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000235:genetics*; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000503:physiopathology; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D014797:Vital Capacity / Q000235:genetics; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human
keywords: COPD; WW domain-containing oxidoreductase; copy number variation; missing heritability