Korean Journal of Clinical Laboratory Science (대한임상검사과학회지)

Korean Society for Clinical Laboratory Science (대한임상검사과학회)
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Association between Tuberculosis Case and CD44 Gene Polymorphism

결핵 발병과 CD44 유전자 다형성사이의 연관성 연구

  • Lim, Hee-Seon (Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University) ;
  • Lee, Sang-In (Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University) ;
  • Park, Sangjung (Department of Biomedical Laboratory Science, College of Life and Health Sciences, Hoseo University)
  • 임희선 (호서대학교 생명보건대학 임상병리학과) ;
  • 이상인 (호서대학교 생명보건대학 임상병리학과) ;
  • 박상정 (호서대학교 생명보건대학 임상병리학과)
  • Received : 2019.05.16
  • Accepted : 2019.06.13
  • Published : 2019.09.30
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Abstract

Tuberculosis, a chronic bacterial infection caused by Mycobacterium tuberculosis (MTB), differs in its status latency and activity because of the characteristics of MTB, immune status of the host, and genetic susceptibility. The host defense mechanism against MTB is caused mainly by interactions between macrophages, T cells, and dendritic cells. CD44 is expressed in activated T cells when infected with MTB and regulates lymphocyte migration. In addition, CD44 mediates leukocyte adhesion to the ECM and plays a role in attracting macrophages and $CD4^+$ T cells to the lungs. Therefore, genetic polymorphism of the CD44 gene will inhibit the host cell immune mechanisms against MTB. This study examined whether the genetic polymorphism of the CD44 gene affects the susceptibility of tuberculosis. A total of 237 SNPs corresponding to the CD44 genes were analyzed using the genotype data of 443 tuberculosis cases and 3,228 healthy controls from the Korean Association Resource (KARE). Of these, 17 SNPs showed a significant association with the tuberculosis case. The most significant SNP was rs75137824 (OR=0.231, CI: 1.51~3.56, $P=1.3{\times}10^{-4}$). In addition, rs10488809, one of the 17 significant SNPs, is important for the tuberculosis outbreak can bind to the JUND and FOS transcription factors and can affect CD44 gene expression. This study suggests that polymorphism of the CD44 gene modulates the host susceptibility to tuberculosis in a variety of ways, resulting in differences in the status of tuberculosis.

결핵균에 의한 만성 세균성 감염인 결핵은 결핵균의 특성, 숙주의 면역상태와 유전적 감수성의 차이에 의해 잠복성과 활동성으로의 진행정도에 차이가 있다. 결핵균에 대한 숙주 방어 기전은 주로 대식세포, T 세포 및 수지상 세포 사이의 상호 작용에 기인한다. CD44는 결핵균에 감염되면 활성 T 세포에서 발현되며 림프구 이동을 조절한다. 또한 CD44는 ECM에 대한 백혈구의 부착을 매개하여 대식세포, CD4+ T cell 등을 폐로 불러모으는 역할을 한다. 따라서, CD44 유전자의 다형성은 결핵균에 대한 숙주세포의 면역기전 저하를 유발할 수 있다. 이 연구의 목적은 CD44 유전자의 유전자 다형성이 결핵의 감수성에 영향을 미치는지 조사하는 것이다. 결핵균과 CD44의 연관성에 대하여 대한 한국 협회 자원의 443명의 cases와 3228명의 control을 이용하여 CD44 유전자의 237개의 SNP를 분석하였다. 이 중 17개의 SNP가 결핵과 통계적으로 유의한 관련성을 보였다. 가장 유의성 있는 SNP는 rs75137824였다(OR=0.231, CI: 1.51~3.56, $P=1.3{\times}10^{-4}$). 또한 결핵 발병에 유의성이 있는 SNP중 rs10488809의 경우는 전사인자 JUND 및 FOS에 결합하는 부위로써 CD44 유전자 발현에 영향을 줄 수 있는 것으로 확인할 수 있었다. 이러한 결과는 결핵 발병이 CD44 발현 차이에 의한 숙주 면역반응에 차이에 의해서 감수성의 차이가 있을 수 있음을 나타 낼 수 있다. 이번 연구 결과는 결핵균 감염에 대한 숙주면역의 유전적 차이가 결핵 진행정도의 차이를 유발할 수 있다는 유전적 배경에 대한 기반을 마련해 줄 수 있을 것이라고 기대한다.

Keywords

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