Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Relations between Polymorphism of NRAMP1 Gene and Susceptibility to Pulmonary Tuberculosis

NRAMP1 유전자 다형성과 폐결핵의 감수성과의 관계

  • Lee, Ji Seok (Department of Internal Medicine, College of Medicine, Pusan National University) ;
  • Cho, Jin Hoon (Department of Internal Medicine, College of Medicine, Pusan National University) ;
  • Kim, Ki Uk (Department of Internal Medicine, College of Medicine, Pusan National University) ;
  • Park, Hye-Kyung (Department of Internal Medicine, College of Medicine, Pusan National University) ;
  • Kim, Yun Seong (Department of Internal Medicine, College of Medicine, Pusan National University) ;
  • Lee, Ho Seok (Department of Thoracic Surgery, College of Medicine, Pusan National University) ;
  • Kim, Yeong Dae (Department of Thoracic Surgery, College of Medicine, Pusan National University) ;
  • Jeon, Doo Soo (Masan National Hospital) ;
  • Park, Seung Kyu (Masan National Hospital) ;
  • Lee, Min Ki (Department of Internal Medicine, College of Medicine, Pusan National University) ;
  • Park, Soon Kew (Department of Internal Medicine, College of Medicine, Pusan National University)
  • 이지석 (부산대학교 의과대학 내과학교실) ;
  • 조진훈 (부산대학교 의과대학 내과학교실) ;
  • 김기욱 (부산대학교 의과대학 내과학교실) ;
  • 박혜경 (부산대학교 의과대학 내과학교실) ;
  • 김윤성 (부산대학교 의과대학 내과학교실) ;
  • 이호석 (부산대학교 의과대학 흉부외과학교실) ;
  • 김영대 (부산대학교 의과대학 흉부외과학교실) ;
  • 전두수 (국립마산병원) ;
  • 박승규 (국립마산병원) ;
  • 이민기 (부산대학교 의과대학 내과학교실) ;
  • 박순규 (부산대학교 의과대학 내과학교실)
  • Received : 2007.04.20
  • Accepted : 2007.05.28
  • Published : 2007.06.30
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Abstract

Background: Several lines of evidence suggest that a host's genetic factors influence the outcome of exposure to Mycobacterium tuberculosis. The aim of this study was to determine whether polymorphism in NRAMP1 (natural resistance associated macrophage protein 1) gene is associated with the susceptibility or resistance to tuberculosis infection for patients with drug-sensitive pulmonary tuberculosis (DS-TB) and multi-drug resistant pulmonary tuberculosis (MDR-TB). Methods: Eight genetic polymorphisms of the NRAMP1 gene were investigated in patients suffering with DS-TB (n=100) or MDR-TB (n=102), and in healthy normal controls (NC, n=96). The genetic polymorphisms of NRAMP1 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of D543N A/G heterogygotes was significantly higher in the DS-TB subjects than the NCs (OR=2.10, 95% CI: 1.00 to 4.41, p=0.049). The frequency of 823C/T T/C heterozygotes was significantly higher in the DS-TB subjects (OR=2.79, 95% CI: 1.11 to 7.04, p=0.029) and the MDR-TB subject (OR=3.30, 95% CI 1.33 to 8.18, p=0.010) than in the NCs. However, the frequency of these genotypes was not different between the DS-TB and MDR-TB subjects. Conclusion: A significant association was found between NRAMP1 823 C/T polymorphism and pulmonary tuberculosis. This result suggests that NRAMP1 polymorphism may be involved in the development of pulmonary tuberculosis in Koreans.

연구배경: 결핵균에 노출된 후 임상적 결핵으로 발병하는데 유전적 인자가 관여할 수 있으며, 치료 반응에도 숙주의 유전적 요인이 관여할 가능성이 있다. 이에 저자들은 NRAMP1 유전자 다형성을 감수성결핵과 다제내성결핵환자로 나누어서 비교하였다. 방 법: 100명의 약제감수성군, 102명의 다제내성군, 96명의 건강대조군을 대상으로 274C/T, 469+14G/C, 577-18G/A, 823C/T, A318V, 1465-85G/A, D543N, 1729+55del4 의 NRAMP1 유전자 다형성의 빈도를 중합효소 연쇄반응기법과 중합효소 연쇄반응-제한분절길이 다형성법을 이용하여 분석하였다. 결 과: NRAMP1 유전자의 D543N 이형접합체의 빈도는 건강대조군에 비해 약제감수성군에서 높았으나(OR=2.10, 95% CI=1.00 to 4.41, p=0.049) 다제내성군에서는 차이가 없었다. 823C/T의 이형접합체의 빈도는 건강대조군에 비해 약제감수성군(OR=2.79, 95% CI=1.11 to 7.04, p=0.029)과 다제내성군 (OR=3.30, 95% CI=1.33 to 8.18, p=0.010)에서 유의하게 높았으나 약제감수성군과 다제내성군 사이에는 유의한 차이가 없었다. 결 론: NRAMP1 유전자의 823C/T 이형접합체의 빈도는 약제감수성군과 다제내성군에서 유의하게 높아, 폐결핵의 발생과 연관되는 후보유전자일 가능성이 있으며 약제감수성결과에 따른 결핵이환에는 차이를 보이지 않았다.

Keywords

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