title: Association of Egr-1 and autophagy-related gene polymorphism in men with chronic obstructive pulmonary disease.
abstract: OBJECTIVE
  Autophagy is important in cellular homeostasis and control of inflammatory immune response. Increased autophagy has recently been associated with increased cell death and chronic obstructive pulmonary disease (COPD) pathogenesis. Two autophagy regulator genes have been identified: Egr-1 (early growth response), associated with different phenotype expressions in asthma; and, Atg16L1 (autophagy related 16-like 1), a candidate gene responsible for susceptibility to chronic inflammatory diseases. We will explore the role of the Egr-1 and Atg16L1 gene polymorphisms in COPD.
  
  
  METHODS
  The genotypes of 151 male smoking patients with COPD and 100 male smoking controls were evaluated by polymerase chain reaction followed by restriction fragment length polymorphism analysis of the Egr-1 (-4071 A → G) rs7729723 and Atg16L-1 (T300A) rs2241880 variants.
  
  
  RESULTS
  The G allele of the Egr-1 gene polymorphism was associated with an increased risk of developing COPD [odds ratio (OR), 2.05; 95% confidence interval (CI), 1.15-3.72], and participants with the G allele polymorphism (GG and GA genotypes) had a 2.56-fold higher risk (OR, 2.56; 95% CI, 1.31-5.16) of having COPD than those homozygous for the A allele [35.8% (54/151) vs. 24.0% (24/100); p = 0.007]. Participants with the A allele of the Atg16L1 gene polymorphism (AA and AG genotypes) had a 3.34-fold higher risk (OR, 3.34; 95% CI, 1.32-8.97) of having COPD than those homozygous for the G allele [93.4% (141/151) vs. 81.0% (81/100); p = 0.013].
  
  
  CONCLUSIONS
  The Egr-1 and Atg16L1 genes' polymorphisms were significant risk factors for susceptibility to COPD. These results demonstrate that autophagy regulator genetic mutations are associated with COPD in male smokers.
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chiung-Zuei
authors.initials: CZ
authors.lastname: Chen
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chih-Ying
authors.initials: CY
authors.lastname: Ou
authors.affiliation: Department of Family Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ru-Hsueh
authors.initials: RH
authors.lastname: Wang
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Cheng-Hung
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chien-Chung
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Han-Yu
authors.initials: HY
authors.lastname: Chang
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, Medical College, National Cheng Kung University, Tainan, Taiwan. Electronic address: hsiue@mail.ncku.edu.tw.
authors.forename: Tzuen-Ren
authors.initials: TR
authors.lastname: Hsiue
mesh_terms: D000368:Aged; D001343:Autophagy / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D051766:Early Growth Response Protein 1 / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D012150:Polymorphism, Restriction Fragment Length; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D012907:Smoking; D013624:Taiwan
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1
keywords: autophagy; chronic obstructive pulmonary disease; polymorphism