title: Association of autophagy related gene polymorphisms with neutrophilic airway inflammation in adult asthma.
abstract: OBJECTIVE
  Role of autophagy in neutrophil function and the association of autophagy and autophagy related (ATG) gene polymorphisms with asthma susceptibility were suggested. In this study, we investigated the genetic association of ATG5 and ATG7 polymorphisms with asthma risk, severity and neutrophilic airway inflammation.
  
  
  METHODS
  We recruited 408 asthma patients and 201 healthy controls. Sputum neutrophil counts were determined by H&E staining. Serum interleukin 8 (IL-8) levels were measured by enzyme-linked immunosorbent assay (ELISA). Genetic polymorphisms of ATG5 (-769T>C, -335G>A, and 8830C>T) and ATG7 (-100A>G and 25108G>C) were genotyped. The functional activities of ATG5 -769T>C and -335G>A variants were investigated by luciferase reporter assays.
  
  
  RESULTS
  No associations of ATG5 and ATG7 polymorphisms with asthma susceptibility and severity were found. ATG5 -769T>C and -335G>A were in complete linkage disequilibrium. In the asthma group, GA/AA genotypes at ATG5 -335G>A were associated with higher neutrophil counts in sputum (p < 0.05); CC/TT genotype at ATG5 8830C>T associated with lower FEV1% predicted value (p < 0.05). DNA fragments containing ATG5 -769T and -335G alleles had higher promoter activities compared to those with -769C and -335A in both human airway epithelial cells (A549, p < 0.01) and human mast cell (HMC-1, p < 0.001). GG and CC genotype at ATG7 -100A>G and 25108G>C were significantly associated with high serum levels of IL-8 (p < 0.05 for both variants).
  
  
  CONCLUSIONS
  Genetic polymorphisms of ATG5 and ATG7 could contribute to neutrophilic airway inflammation in the pathogenesis of adult asthma.
authors.affiliation: Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Korea ; Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Duy Le
authors.initials: DL
authors.lastname: Pham
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Molecular Biology and Genetics, Health Sciences University of Mongolia, Ulaanbaatar, Mongolia.
authors.forename: Purevsuren
authors.initials: P
authors.lastname: Losol
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Yang
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Yoo Seob
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Ye
authors.affiliation: Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Korea ; Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Hae-Sim
authors.initials: HS
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001343:Autophagy / Q000235:genetics*; D000071187:Autophagy-Related Protein 5 / Q000235:genetics*; D000071193:Autophagy-Related Protein 7 / Q000235:genetics*; D016022:Case-Control Studies; D002460:Cell Line; D005260:Female; D005787:Gene Frequency; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D020556:Neutrophil Infiltration / Q000235:genetics*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D012720:Severity of Illness Index; D014162:Transfection; D055815:Young Adult
chemical_list: C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; C508606:CXCL8 protein, human; D016209:Interleukin-8; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7
keywords: Asthma; Autophagy; Neutrophils; Polymorphism, genetic