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소음성 난청에서의 Mitochondrial DNA A3243G, A1555G, A7445G 돌연변이

Mitochondrial DNA Mutation (3243A→G,1555A→4G,7445A→G) in Noise-Induced

  • 홍영습 (동아대학교 의과대학 예방의학교실 및 암분자치료연구센터) ;
  • ;
  • 이명진 (고베의과대학 공중보건학교실) ;
  • 곽기영 (동아대학교 의과대학 예방의학교실 및 암분자치료연구센터) ;
  • 황찬호 (동아대학교 의과대학 이비인후과교실) ;
  • 신동훈 (계명대학교 의과대학 예방의학교실) ;
  • 곽종영 (동아대학교 암분자치료연구센터) ;
  • 이용환 (고신대학교 의과대학 예방의학교실) ;
  • 김종민 (동아대학교 의과대학 해부학교실) ;
  • 김준연 (동아대학교 의과대학 예방의학교실 및 환경유전역학 연구회)
  • Hong Young-Seoub (Department of Preventive Medicine, College of Medicine, Dong-A University, Medical Research Center for Cancer Molecular Therapy) ;
  • Nishio Hisahide (Department of Public Health, Kobe University School of Medicine) ;
  • Lee Myeong-Jin (Department of Public Health, Kobe University School of Medicine) ;
  • Kwak Ki-Young (Department of Preventive Medicine, College of Medicine, Dong-A University, Medical Research Center for Cancer Molecular Therapy) ;
  • Hwang Chan-Ho (Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Dong-A University) ;
  • Shin Dong-Hoon (Department of Preventive Medicine, College of Medicine, Keimyung University) ;
  • Kwak Jong-Young (Medical Research Center for Cancer Molecular Therapy, College of Medicine, Dong-A University) ;
  • Lee Yong-Hwan (Department of Preventive Medicine, Kosin Medical College) ;
  • Kim Jong-Min (Department of Anatomy and Cell Biology, College of Medicine, Dong-A University) ;
  • Kim Joon-Youn (Department of Preventive Medicine, College of Medicine, Dong-A University, The Research Society of Environmental Genetic Epidemiology)
  • 발행 : 2004.12.01

초록

본 연구는 소음성 감각신경성난청 환자의 유전적 관련요인을 파악하고자 관련성이 의심되는 mitochondrial DNA의 돌연변이와 소음성 감각신경성난청과의 관련성을 조사하였다. 말초혈액 백혈구로부터 DNA를 추출한 후, mtDNA 3243, 1555, 7445부위의 $A{\rightarrow}G$ 돌연변이 유무를 관찰하기 위하여 mtDNA 3243, 1555, 7445부위 가 포함된 mtDNA fragment를 중합효소 연쇄반응으로 증폭하고 유전자 제한효소로 소화하여 전기영동하고 ethidium bromide 용액으로 염색하여 UV transilluminator에서 관찰하였다. 그리고, PCR 산물을 이용하여 DNA 염기서열을 분석하여 mtDNA 3243, 1555, 7445부 위에서의 염기서열 분석을 실시하여 mtDNA 3243, 1555, 7445부위 의 $A{\rightarrow}G$ 돌연변이를 관찰하였다 MtDNA A3243G, A1555G, A7445G의 돌연변이를 관찰한 결과 돌연변이 부위가 포함된 fragment가 소음성 감각신경성난청 환자군, 감각신경성난청 환자군, 대조군 모두에서 증폭됨을 관찰하였다. 또한 PCR 산물을 제한효소로 처 리 한 결과에서도 mtDNA에서 3243, 1555, 7445부위의 $A{\rightarrow}G$ 돌연변이가 일어나지 않았음을 알 수 있었다. PCR산물을 이용하여 DNA 염기서열을 분석하여 mtDNA 3243, 1555, 7445부위에서의 염기서열을 확인한 결과 이미 밝혀진 사람의 mtDNA 3243, 1555, 7445부 위의 염기서열과 동일한 염기서열임이 확인되었으므로 mtDNA 3243, 1555, 7445부위의 $A{\rightarrow}G$ 돌연변이가 일어나지 않았음을 확인하였다. 소음성 감각신경성난청과 mtDNA 3243, 1555, 7445부위의 $A{\rightarrow}G$ 돌연변이와는 관련이 없는 것으로 관찰되었다.

Mitochondrial DNA mutations have been reported in recent years in association with sensorineural hering loss. The purpose of this study is to identify the association between the noise-induced sensorineural hearing loss and the A to G mutation at nucleotide 3243, 1555, 7445 of mitochondrial DNA. Study subjects were established by history and chart review, and audiological and clinical data were obtained. Blood was sampled from 214 normal controls, 102 noise-induced hearing loss, and 28 sensorineural hearing loss. The DNA of these individuals were extracted, and mitochondrial DNA fragments were analyzed by polymerase chain reaction. Subsequently, the coding sequence of mitochondrial DNA 3243, 1555, 7445 were sequenced, and compared to the normal sequence, and all sequence variations were analyzed by restriction enzymes. Mitochondrial DNA mutations $(3243A{\rightarrow}G,\;1555A{\rightarrow}4G,\;7445A{\rightarrow}G)$ were not detected by polymerase chain reactions in any patients with noise-induced hearing loss, sensorineural hearing loss, and normal controls. The DNA sequencing of PCR products did not revealed an A to G substitution at nucleotide 3243, 1555, 7445 of mitochondrial DNA. The noise-induced sensorineural hearing loss was not associated with mitochondrial DNA mutation $(3243A{\rightarrow}G,\;1555A{\rightarrow}4G,\;7445A{\rightarrow}G)$.

키워드

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