Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Polymorphisms of tumor necrosis factor-alpha promotor gene in Kawasaki disease and relation to the risk of coronary artery lesion

가와사키병에서의 TNF-alpha 유전자의 다형성 및 관상동맥 합병증과의 연관성

  • Kim, Se-hwa (Department of Pediatrics, College of Medicine, Konyang University) ;
  • Yun, Jang-won (Department of Pediatrics, College of Medicine, Konyang University) ;
  • Lee, Young-hyuk (Department of Pediatrics, College of Medicine, Konyang University) ;
  • Cheon, Eun-jung (Department of Pediatrics, College of Medicine, Konyang University)
  • 김세화 (건양대학교 의과대학 소아과학교실) ;
  • 윤장원 (건양대학교 의과대학 소아과학교실) ;
  • 이영혁 (건양대학교 의과대학 소아과학교실) ;
  • 천은정 (건양대학교 의과대학 소아과학교실)
  • Received : 2008.08.25
  • Accepted : 2009.02.06
  • Published : 2009.04.15
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Abstract

Purpose : The purpose of this study was to investigate the polymorphisms of the TNF-alpha promotor gene, its susceptibility to Kawasaki disease (KD) and to assess whether the TNF-alpha promotor gene polymorphism was related the risk of coronary artery lesions (CALs). Methods : From January 2003 to January 2007, 51 children (30 boys and 21 girls) with KD and 48 children forming an age-matched control group were studied. DNA from the peripheral blood of all the children was sampled, and the DNA polymorphisms of the 5' flanking regions of the TNF-alpha promoter gene at position -308 [guanine (G) to adenine (A)] were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Then, the relationship between KD and the TNF-alpha promotor gene polymorphisms was evaluated. Results : The A allele frequency of the -308 site of the TNF-alpha promotor gene was 17.6% (9/51) for children with KD and 6.8% (3/48) for the control group children, but this result was not statistically significant. Twenty-four patients experienced CALs within 60 days after the onset of symptoms. KD children with TNF-alpha -308 A allele had lower frequencies of CALs (12.5% versus 22.2%, P>0.05). Conclusion : The DNA polymorphism of the -308 site TNF-alpha gene was not associated with susceptibility to KD and a risk of CALs. Multicenter, large-scale randomized controlled trials are needed for further study.

목 적 : 저자들은 가와사키병 환아에서 TNF-alpha 유전자의 다형성을 조사함으로써 가와사키병과 유전자 다형성의 관련 여부를 알아보고, 또한 관상동맥 병변의 발생과 연관이 있는지를 살펴보려 하였다. 방 법 : 2003년 1월부터 2007년 1월까지 가와사키병 환아 51명과 대조군 48명을 대상으로 TNF-alpha 촉진자의 단일 유전자 다형성을 살펴보았으며, 가와사키병 환아 중 관상동맥 병변이 있는 24명(관상동맥병변군)과 관상동맥 이상이 없었던 27명(정상관상동맥군)에서의 유전자 다형성을 또한 비교하였다. 말초 혈액에서 DNA를 추출하여 TNF-alpha 유전자 -308 부위의 촉진자에 위치한 2개의 단일 염기 서열 G/A에 대한 대립 유전자의 다형성을 Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) 방법으로 분석하였다. 결 과 : 가와사키병 환아군에서의 -308번 TNF-alpha 유전자의 다형성은 51명 중 9명으로 17.6%였고, 정상 대조군에서는 48명 중 3명으로 6.8%로 가와사키병 환아군에서 높았으나 통계학적으로 유의성은 없었다. 가와사키병 환아 중 관상동맥병병군 24명 중 3명인 12.5%에서 유전자 다형성이 있었고 정상관상동맥군은 27명 중 6명인 22.2%로 정상관상동맥군에서 더 높은 빈도 이었으나 통계학적으로 유의하지 않았다. 결 론 : 본 연구에서는 가와사키병 환아의 TNF-alpha의 다형성과 가와사키병의 발병과의 관련성이 통계학적으로 유의한 수준은 아니지만 가와사키병 환아에서 G/A 빈도수가 17.6%으로 대조군에서 6.8% 보다 다소 높게 나타난 결과를 얻었고 앞으로 많은 수의 환아를 대상으로 한다면 유의한 차이가 있을 것으로 생각되므로 향후 대규모의 지속적인 연구가 필요할 것이다.

Keywords

Acknowledgement

Supported by : Seoul University Pediatrics

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