Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
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가와사키병의 관상동맥 이상과 catechol-O-methyltransferase 유전자의 단일염기다형성

The relationship between catechol-O-methyltransferase gene polymorphism and coronary artery abnormality in Kawasaki disease

  • 이효진 (성애병원 소아청소년과) ;
  • 이명숙 (성애병원 소아청소년과) ;
  • 김지숙 (성애병원 소아청소년과) ;
  • 김은령 (성애병원 소아청소년과) ;
  • 강성욱 (경희대학교 고황의학연구소) ;
  • 김수강 (경희대학교 고황의학연구소) ;
  • 정주호 (경희대학교 고황의학연구소) ;
  • 윤경림 (경희대학교 동서신의학병원 소아과청소년과) ;
  • 한미영 (경희대학교 의과대학 소아과학교실) ;
  • 차성호 (경희대학교 의과대학 소아과학교실)
  • Lee, Hyo Jin (Department of Pediatrics, Sung-Ae General Hospital) ;
  • Lee, Myung Sook (Department of Pediatrics, Sung-Ae General Hospital) ;
  • Kim, Ji Sook (Department of Pediatrics, Sung-Ae General Hospital) ;
  • Kim, Eun Ryoung (Department of Pediatrics, Sung-Ae General Hospital) ;
  • Kang, Sung Wook (Kohwang Medical Research Institute, School of Medicine, Kyunghee University) ;
  • Kim, Soo Kang (Kohwang Medical Research Institute, School of Medicine, Kyunghee University) ;
  • Chung, Joo Ho (Kohwang Medical Research Institute, School of Medicine, Kyunghee University) ;
  • Yoon, Kyung Lim (Department of Pediatrics, East-West Neo-medical Center, Kyunghee University) ;
  • Han, Mi Young (Department of Pediatrics, College of Medicine, Kyunghee University) ;
  • Cha, Seong Ho (Department of Pediatrics, College of Medicine, Kyunghee University)
  • 투고 : 2008.07.04
  • 심사 : 2008.09.04
  • 발행 : 2009.01.15
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초록

목 적 : 가와사키병은 극동아시아인에서 다른 인종보다 높은 발생빈도를 보이고 여러 유전자 다형성이 보고되고 있다. COMT 는 염색체 22q11에 위치한 유전자로 메틸기접합을 촉진시켜 도파민, 에피네프린, 노르에피네프린 같은 카테콜아민 신경전달 물질을 불활성화 시키는 역할을 한다. COMT 유전자의 다형성은 estradiol 대사와 연관되어 혈압과 심근경색 등 심장질환과의 연관성이 보고되었고, 급성 관상동맥 질환과 관련이 있다고 보고되었다. 이 연구에서는 가와사키병에서 관상동맥 확장과 COMT 유전자 다형성과의 연관성을 알아보고자 하였다. 방 법 : 가와사키병 환자군 101명과 대조군 306명으로부터 혈액 2 mL를 채취하여 DNA를 분리하였으며, PCR 방법으로 COMT 유전자의 rs4680과 rs769224의 Guanine에서 Adenine으로의 단일염기다형성(SNP)을 분석하였다. 환자군 중 관상동맥의 확장을 동반한 37명과 관상동맥 확장이 없는 62명 대상으로 COMT 유전자의 단일염기다형성에 대한 관련성을 확인하였다. 결과 : 가와사키병 환자군과 대조군 사이에 COMT 유전자의 연관성은 보이지 않았다. COMT 유전자의 rs4680에서 가와사키병 환자군 중 관상동맥 확장을 가진 37명은 유전형 G/G (Val158 Val)는 19명(51.4%), G/A(Val158Met)는 13명(35.1%), A/A (Met158Met)는 5명(13.5%)이었고 관상동맥 확장이 없는 62명에서는 G/G (Val158Val)는 34명(54.8%), G/A (Val158Met)는 25명(40.3%), A/A (Met158Met)는 3명(4.8%)으로 통계학적 유의성이 없었으나(codominant P=0.32, dominant P=0.74, recessive P=0.13), rs769224에서는 관상동맥 확장을 가진 37명은 유전형 G/G는 30명(81.1%), G/A는 6명(16.2%), A/A는 1명(2.7 %)이었고 관상동맥 확장이 없는 62명에서는 G/G는 61명(98.4 %), G/A 1명(1.6%), A/A 0명(0.0%)으로 codominant와 dominant 모델에서 통계학적 유의성이 있었다(codominant P=0.0077, dominant P=0.0021, recessive P=0.16). 결론 : COMT 유전자의 단일염기다형성은 가와사키병과의 연관성은 보이지 않았고, rs4680 다형성과 관상동맥 확장은 연관성을 보이지 않았으나 rs769224 다형성과 관상동맥 확장은 통계학적으로 의미있게 연관성이 있었다.

Purpose : Many gene polymorphisms are associated with coronary artery abnormalities in Kawasaki disease. Catechol-O- methyltransferase (COMT) plays an important role in the metabolism of catecholamines, catechol estrogen, and catechol drugs. Polymorphisms of the COMT gene are reported to be associated with myocardial infarction and coronary artery abnormalities. The aim of this study was to evaluate the relationship between COMT gene polymorphisms and coronary artery abnormalities in Kawasaki disease patients. Methods : One hundred and one Korean children with Kawasaki disease and 306 healthy Korean control subjects were enrolled in this study. The polymorphisms of the COMT gene were analyzed by direct sequencing. Results : There were no differences in the genotype and allelic frequency of the rs4680 and rs769224 polymorphic sites between Kawasaki disease and control subjects. Further, no significant difference was found in the rs4680 polymorphism between patients with coronary artery abnormalities and patients without coronary artery abnormalities (codominant P=0.32, dominant P=0.74, recessive P=0.13). However, the distribution of the rs769224 polymorphism was significantly different between patients with coronary artery abnormalities and patients without coronary artery abnormalities (codominant P= 0.0077, dominant P=0.0021, recessive P=0.16). Conclusion : Our results indicate that the polymorphisms of the rs769224 gene might be related to the development of coronary artery abnormalities in Kawasaki disease.

키워드

참고문헌

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