title: Rare variant of MAP2K7 is associated with increased risk of COPD in southern and eastern Chinese.
abstract: A wide range of common loci have been extensively screened and evaluated for their associations with various complex diseases; however, the relevance of rare variants causing missense substitutions in the protein-coding genes in human diseases is still poorly understood.
  
  
  
  In this study, we conducted a two-stage retrospective study of a total of 1791 patients with COPD and 1940 controls in southern and eastern Chinese to test relevancies of five rare variants (i.e. p.Glu116Lys, p.Asn118Ser, p.Arg138Cys, p.Ala195Thr and p.Leu259Phe) of human mitogen-activated protein kinase kinase 7 (MAP2K7) to COPD susceptibility. The effects of these loci on lung function were further estimated.
  
  
  
  The p.Glu116Lys rare variant had significant associations with COPD risk. Compared to individuals with Glu/Glu wild-genotype, those with 116Lys rare variants (Lys/Glu+Lys/Lys) had an increased risk of COPD (OR = 3.83, 95% CI: 2.64-5.56; P = 1.45 × 10-12). Meanwhile, the carriers with 116Lys rare variants (Lys/Glu+Lys/Lys) had lower pre-forced expiratory volume in 1 s (pre-FEV1: 1.74 ± 0.70 vs 2.00 ± 0.68; P = 3.97 × 10-5) and lower pre-FEV1to pre-forced vital capacity ratio (pre-FEV1/FVC: 0.68 ± 0.14 vs 0.75 ± 0.12; P = 2.40 × 10-10) than those with Glu/Glu genotype. However, for other rare variants, no significant association with either COPD risk or lung function was observed.
  
  
  
  Our data strongly suggest that the p.Glu116Lys rare variant in MAP2K7 predisposes its carriers to develop COPD, which would provide a useful genetic biomarker for COPD susceptibility in Chinese.
authors.affiliation: Biomedicine Research Center of The Third Affiliated Hospital of GMU, 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: Biomedicine Research Center of The Third Affiliated Hospital of GMU, 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: Yinyan
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Arts and Sciences, Colby-Sawyer College, New London, New Hampshire, USA.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Lu
authors.affiliation: Biomedicine Research Center of The Third Affiliated Hospital of GMU, 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: Chenli
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Environmental Health, Guangxi Medical University, Nanning, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Nong
authors.affiliation: Biomedicine Research Center of The Third Affiliated Hospital of GMU, 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: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Biomedicine Research Center of The Third Affiliated Hospital of GMU, 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: Jiansong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Biomedicine Research Center of The Third Affiliated Hospital of GMU, 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: Department of Genetics, Medical College of Soochow University, Suzhou, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Biomedicine Research Center of The Third Affiliated Hospital of GMU, 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: D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D048688:MAP Kinase Kinase 7 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D048688:MAP Kinase Kinase 7; C482569:MAP2K7 protein, human
keywords: case-control study; chronic obstructive pulmonary disease; mitogen-activated protein kinase kinase 7; rare variant; susceptibility