The Korean journal of internal medicine

  • 제31권2호
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  • Pages.375-385
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  • 2016
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  • 1226-3303(pISSN)
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  • 2005-6648(eISSN)
대한내과학회 (The Korean Association of Internal Medicine)
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Association of autophagy related gene polymorphisms with neutrophilic airway inflammation in adult asthma

  • Pham, Duy Le (Department of Biomedical Sciences, Ajou University School of Medicine) ;
  • Kim, Seung-Hyun (Department of Allergy and Clinical Immunology, Ajou University School of Medicine) ;
  • Losol, Purevsuren (Department of Molecular Biology and Genetics, Health Sciences University of Mongolia) ;
  • Yang, Eun-Mi (Department of Allergy and Clinical Immunology, Ajou University School of Medicine) ;
  • Shin, Yoo Seob (Department of Allergy and Clinical Immunology, Ajou University School of Medicine) ;
  • Ye, Young-Min (Department of Allergy and Clinical Immunology, Ajou University School of Medicine) ;
  • Park, Hae-Sim (Department of Biomedical Sciences, Ajou University School of Medicine)
  • 투고 : 2014.12.26
  • 심사 : 2015.08.17
  • 발행 : 2016.03.01
⟨ 이전 논문 다음 논문 ⟩

초록

Background/Aims: 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.

키워드

과제정보

연구 과제 주관 기관 : Ministry of Health and Welfare

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