Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Intratypic Variants of HPV-16 E6jE7 Oncogene Isolated from Sexually High-Risk Women in Busan.

부산지역 유흥업소 종사여성으로부터 분리된 HPV16형의 발암유전자(E6/E7) 돌연변이 유형 분석

  • Min, Sang-Kee (Division of Epidemiology, Busan Institute of Health and Environment) ;
  • Kim, Sung-Soon (Divison of AIDS, Center for Immunology and Pathology, National Institute of Health, Korea Center for Disease Control & Prevention) ;
  • Choi, Byeong-Sun (Divison of AIDS, Center for Immunology and Pathology, National Institute of Health, Korea Center for Disease Control & Prevention) ;
  • Jang, Dai-Ho (Divison of AIDS, Center for Immunology and Pathology, National Institute of Health, Korea Center for Disease Control & Prevention) ;
  • Lee, Mee-Ok (Division of Epidemiology, Busan Institute of Health and Environment) ;
  • Choi, Seung-Hwa (Division of Epidemiology, Busan Institute of Health and Environment) ;
  • Kim, Nam-Ho (Division of Epidemiology, Busan Institute of Health and Environment) ;
  • Park, Yon-Koung (Division of Epidemiology, Busan Institute of Health and Environment) ;
  • Jeong, Yeong-A (Division of Epidemiology, Busan Institute of Health and Environment) ;
  • Kim, Seong-Joon (Division of Epidemiology, Busan Institute of Health and Environment) ;
  • Bin, Jae-Hun (Division of Epidemiology, Busan Institute of Health and Environment) ;
  • Park, Ho-Kuk (Division of Epidemiology, Busan Institute of Health and Environment)
  • 민상기 (부산광역시보건환경연구원) ;
  • 김성순 (질병관리본부 국립보건연구원 면역병리센터 에이즈 종양바이러스팀) ;
  • 최병선 (질병관리본부 국립보건연구원 면역병리센터 에이즈 종양바이러스팀) ;
  • 장대호 (질병관리본부 국립보건연구원 면역병리센터 에이즈 종양바이러스팀) ;
  • 이미옥 (부산광역시보건환경연구원) ;
  • 최성화 (부산광역시보건환경연구원) ;
  • 김남호 (부산광역시보건환경연구원) ;
  • 박연경 (부산광역시보건환경연구원) ;
  • 정영아 (부산광역시보건환경연구원) ;
  • 김성준 (부산광역시보건환경연구원) ;
  • 빈재훈 (부산광역시보건환경연구원) ;
  • 박호국 (부산광역시보건환경연구원)
  • Published : 2009.06.30
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Abstract

Recent studies have reported that the distribution of HPV-16 sequence variation differs geographically, and more specifically that HPV-16 E6/E7 intratypic variants might carry a high risk for development of ICC (invasive cervical cancer) and CIN (cervical intraepithelial neoplasia) in a given population. To investigate the genetic diversities of HPV-16 E6/E7 oncogene by region, we collected nineteen HPV-16 isolates from sexually high-risk women in Busan, and analyzed the HPV-16 E6/E7 coding regions (nt 34 to 880) with HPV-16 E6/E7 specific PCR amplification. At the nucleotide levet eleven variants of the E6 genes and nine variants of the E7 genes were identified as follows: E6 T178G (n=l1), E6 T178A (n=l), E6 T350G (n=3), E6 A442C (n=2), E6 AI04T, E6 All1G, E6 C116T, E6 G145T, E6 T183G, E6 C335T, E6 G522C and E7 A647G (n=12), E7 A645C, E7 A777C, E7 G663A, E7 T732C, E7 T760C, E7 A775T, E7 T789C and E7 T795G, respectively. At the amino acid levet the isolated HPV-16 E6 and E7 genes showed eleven E6 variants: E6 D25E (n=12), E6 L83V (n=4), E6 E113D (n=2), E6 MIL, E6 Q3R, E6 P5S, E6 Q14H, E6 D25N, E6 127R, E6 H78Y, E6 C140S and three E7 variants: N29S (n=12), L28F, T72S. HPV16 E6 L83V, the dominant variant in the Caucasian population, showed relatively low frequencies in our study population. We elucidated that the dominant HPV-16 E6/E7 variants were HPV-16 E6 D25E (63.2%) and HPV-16 E7 N29S (63.2%), which were phylogenetically included in Asian lineage. Further study is needed to evaluate the risk of cervical cancer related HPV-16 E6/E7 intratypic variants in the Korean population.

HPV-16형의 염기배열 변이는 지역적, 인종적으로 특징적인 차이가 있으며 특히 HPV-16형 E6/E7 유전자의 특정 염기 서열변이는 자궁경부암 및 자궁상피내 신생종양물의 발생을 일으키는 고위험 요인으로 알려져 있다. 본 연구는 2007년 부산지역 유흥업소 종사여성으로 분리된 HPV-16형 19건을 대상으로 E6/E7 유전자 영역(nt 34-880)을 표적으로 지역적 염기 서열 변이를 조사하였다. nucleotide 수준에서 HPV16형 E6 유전자는 T178G (n=11), T178A (n=1), T350G (n=4), A442C (n=2), A104T, A111G, C116T, G145T, T183G, C335T, G522C 등 11종의 변이주가 발견되었고, E7 유전자는 A647G (n=12), A645C, A777C, G663A, T732C, T760C, A775T, T789C, T795G 등 9종의 변이주가 발견되었다. 아미노산 수준에서는 HPV-16형 E6 단백질의 경우 D25E (n=12), L83V (n=4), E113D (n=2), MIL, Q3R, P5S, Q14H, D25N, 127R, H78Y, C140S 등 11종의 변이주를, HPV16형 E7 단백질의 경우 N29S (n=12), L28F, T72S 등 3종의 변이주를 관찰할 수 있었다. 본 연구 결과, 부산지역의 HPV-16형 E6/E7 우점 돌연변이주는 E6 D25E (75%), E7 N29S (78%)로 각각 나타났다. 앞으로 자궁경부암 환자 및 일반여성을 포함한 더 많은 모집 단을 대상으로 HPV-16형 E6/E7의 intratypic variants를 비교 조사하여 실제 HPV-16형 E6/E7 어떤 변이주가 자궁경부암 유발 위험성과의 관련성은 더 많이 연구되어져야 할 것으로 사료된다.

Keywords

References

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