Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Lack of the Association between Microsatellite Polymorphism in Toll-like Receptor 2 Gene and Development of COPD

Toll-like Receptor 2 유전자의 Microsatellite 유전자 다형성과 만성폐쇄성폐질환 발생과의 연관성 결여

  • Lee, Hee Seok (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Lee, Hye Won (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Kim, Deog Kyeom (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Ko, Dong Seok (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Park, Gun Min (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Hwang, Yong Il (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Lee, Sang-Min (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Yoo, Chul Gyu (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Kim, Young Whan (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Han, Sung Koo (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Shim, Young-Soo (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine) ;
  • Yim, Jae-Joon (Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine)
  • 이희석 (서울대학교 의과대학 내과학교실 및 폐 연구소) ;
  • 이혜원 (서울대학교 의과대학 내과학교실 및 폐 연구소) ;
  • 김덕겸 (서울대학교 의과대학 내과학교실 및 폐 연구소) ;
  • 고동석 (서울대학교 의과대학 내과학교실 및 폐 연구소) ;
  • 박근민 (서울대학교 의과대학 내과학교실 및 폐 연구소) ;
  • 황용일 (서울대학교 의과대학 내과학교실 및 폐 연구소) ;
  • 이상민 (서울대학교 의과대학 내과학교실 및 폐 연구소) ;
  • 유철규 (서울대학교 의과대학 내과학교실 및 폐 연구소) ;
  • 김영환 (서울대학교 의과대학 내과학교실 및 폐 연구소) ;
  • 한성구 (서울대학교 의과대학 내과학교실 및 폐 연구소) ;
  • 심영수 (서울대학교 의과대학 내과학교실 및 폐 연구소) ;
  • 임재준 (서울대학교 의과대학 내과학교실 및 폐 연구소)
  • Received : 2005.01.17
  • Accepted : 2005.03.07
  • Published : 2005.04.30
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Abstract

Background : The fact that only 10-20% of chronic cigarette smokers develop chronic obstructive pulmonary disease (COPD) reflects the presence of genetic factors associated with the susceptibility to COPD. Recently, it was reported that the surfactant protein A increases the secretion of matrix metalloprotease 9, which degrades extracellular matrices of the lung, through a Toll-like receptor 2 (TLR2). In this context, possible role of TLR2 in the pathogenesis of COPD was postulated, and a functional dinucleotide repeat polymorphism in intron II of TLR2 was evaluated for any association with COPD. Method : Male patients with COPD and male smokers with a normal pulmonary function were enrolled in this study. The number of Guanine-Thymine repeats in intron II of the TLR2 gene were counted. Because the distributions of the repeats were trimodal, the alleles were classified into three subclasses, 12-16 repeats: short (S) alleles; 17-22 repeats: medium length (M) alleles; and 23-27 repeats: long (L) alleles. Result : 125 male patients with COPD and 144 age- and gender-matched blood donors with a normal lung function were enrolled. There were no differences in the distribution of each allele subclass (S, M and L) between the COPD and control group (p=0.75). The frequencies of the genotypes with and without each allele subclass in the COPD and control group were similar. Conclusion : A microsatellite polymorphism in intron II of TLR2 gene was not associated with the development of COPD in Koreans.

연구배경 : 장기간 흡연을 하는 사람의 10-20%에서만 COPD가 발생한다는 사실은 COPD의 발생에 유전적 인자가 관여함을 시사한다. 최근 surfactant protein A가, COPD의 병인에 중요한 역할을 하는 것으로 알려진 MMP-9의 분비를 TLR2를 통해 증가시킨다고. 그러므로 COPD의 병인에 TLR2이 역할을 할 수 있을 것이라는 가정 아래, TLR2 유전자의 intron II에 존재하는 Guanine-Thymine (GT)의 반복으로 이루어진 유전자다형성과 한국인에서의 COPD의 발생과의 연관성을 규명하고자 하였다. 방 법 : 흡연력이 있는 남자 COPD 환자와 정상 폐기능을 보이는 남자 흡연자를 대상으로 하여, TLR2 유전자의 intron II의 GT 반복횟수를 확인하였다. 그 GT 반복이 3상성의 분포를 보여 이들을 다시 세 개의 맞섬 유전자 아형으로 분류하여 분석하였다. (12-16회 GT 반복: 짧은 아형; 17-22회 반복: 중간 아형; 23-27회 반복: 긴 아형) 결 과 : 각각의 맞섬유전자 아형의 분포는 125명의 COPD군과 144명의 대조군 사이에 유의한 차이는 없었다(P=0.75). 또한 각각의 맞섬유전자 아형의 유무에 따른 유전형의 빈도도 두 군간의 차이는 관찰할 수 없었다. 결 론 : TLR2 유전자의 intron II에 존재하는 GT 반복으로 이루어진 유전자다형성은 한국인에서 COPD의 발생과 연관되어 있지 않다.

Keywords

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