한국인 다낭성 난소증후군 환자에서 $CYP11{\alpha}$ 유전자 $(tttta)_n$ 다형성 양상 및 역할

$CYP11{\alpha}$ $(tttta)_n$ Microsatellite Polymorphism in Korean Patients with Polycystic Ovary Syndrome

  • 김진주 (서울대학교 의과대학 산부인과학교실) ;
  • 최영민 (서울대학교 의과대학 산부인과학교실) ;
  • 윤상호 (서울대학교 의과대학 산부인과학교실) ;
  • 정선하 (서울대학교 의과대학 산부인과학교실) ;
  • 최두석 (성균관대학교 의과대학 산부인과학교실) ;
  • 구승엽 (서울대학교 의과대학 산부인과학교실) ;
  • 지병철 (서울대학교 의과대학 산부인과학교실) ;
  • 서창석 (서울대학교 의과대학 산부인과학교실) ;
  • 김석현 (서울대학교 의과대학 산부인과학교실) ;
  • 김정구 (서울대학교 의과대학 산부인과학교실) ;
  • 문신용 (서울대학교 의과대학 산부인과학교실)
  • Kim, Jin-Ju (Department of Obstetrics and Gynecology, Seoul National University College of Medicine) ;
  • Choi, Young-Min (Department of Obstetrics and Gynecology, Seoul National University College of Medicine) ;
  • Yoon, Sang-Ho (Department of Obstetrics and Gynecology, Seoul National University College of Medicine) ;
  • Choung, Seon-Ha (Department of Obstetrics and Gynecology, Seoul National University College of Medicine) ;
  • Choi, Doo-Seok (Department of Obstetrics and Gynecology, Sungkyunkwan University School of Medicine) ;
  • Ku, Seung-Yup (Department of Obstetrics and Gynecology, Seoul National University College of Medicine) ;
  • Jee, Byung-Chul (Department of Obstetrics and Gynecology, Seoul National University College of Medicine) ;
  • Suh, Chang-Suk (Department of Obstetrics and Gynecology, Seoul National University College of Medicine) ;
  • Kim, Seok-Hyun (Department of Obstetrics and Gynecology, Seoul National University College of Medicine) ;
  • Kim, Jung-Gu (Department of Obstetrics and Gynecology, Seoul National University College of Medicine) ;
  • Moon, Shin-Yong (Department of Obstetrics and Gynecology, Seoul National University College of Medicine)
  • 발행 : 2004.12.30

초록

Objectives: To investigate the distribution and functional significance of $CYP11{\alpha}$ $(tttta)_n$ microsatellite polymorphism in Korean patients with polycystic ovary syndrome Materials and Methods: Analysis of $CYP11{\alpha}$ $(tttta)_n$ microsatellite polymorphism was carried out on DNA samples from 97 patients with polycystic ovary syndrome and 70 normal controls. Comparison were done between PCOS patients and controls concerning $CYP11{\alpha}$ $(tttta)_n$ microsatellite polymorphism genotype or allele frequencies. Results: The most frequent allele observed in the controls was an allele with six repeats (60.7%). Significant difference in the frequency of genotype (4R (-) genotype) having no copy of four-repeatallele were observed between PCOS patients and controls (66.0% vs 34.0%, p=0.038, OR=1.939). But no significant difference was observed in the serum levels of total testosterone or free testosterone between 4R (+) genotype and 4R (-) genotype among PCOS patients. However, hyperandrogenic PCOS patients with 4R (+) genotype showed a higher serum testosterone levels compared to controls (mean $\pm$ S.D: $0.49{\pm}0.21\;ng/ml$ vs $0.37{\pm}0.18\;ng/ml$, p=0.037). Conclusion: The alleleic distribution of $CYP11{\alpha}$ $(tttta)_n$ microsatellite polymorphism in Korean subjects were different from those reported in Caucasians. $CYP11{\alpha}$ $(tttta)_n$ microsatellite polymorphism was associated with polycystic ovary syndrome in the Korean population, and may play a role in the synthesis of androgens in patients with polycystic ovary syndrome.

키워드

참고문헌

  1. Franks S, Gharani N, Waterworth D, et al. The genetic basis of polycystic ovary syndrome. Hum Reprod 1997; 12: 2641-8 https://doi.org/10.1093/humrep/12.12.2641
  2. Gharani N, Waterworth DM, Batty S, et al. Association of the steroid synthesis gene $CYP11{\alpha}$ with po-lycystic ovary syndrome and hyperandrogenism. Hum Mol Genet 1997; 6(3): 397-402 https://doi.org/10.1093/hmg/6.3.397
  3. Kandarakis ED, Bartzis MI, Bergiele AT, et al. Microsatellite polymorphism (tttta)$_{n}$ at 528 base pairs of gene CYP11$\alpha$ influences hyperandrogenemia in parients with polycystic ovary symdrome. Fertil Steril 2000; 73: 735-41. https://doi.org/10.1016/S0015-0282(99)00628-7
  4. Balen AH, Laven JSE, Tan SL, et al. Ultrasound asse-ssment of the polycystic ovary: International conse-nsus definitions. Human Reprod Update 2003; 9: 505-14 https://doi.org/10.1093/humupd/dmg044
  5. Moore CCD, Brentano ST, Miller WL. Human P450-scc gene transcription is induced by cyclic AMP and repressed by 12-O-tetradecanoylphorbol-13-acetate and A23817 through independent cis elements. Mol Cell Biol 1990; 10: 6013-23 https://doi.org/10.1128/MCB.10.11.6013
  6. Waterworth DM, Bennett ST, Gharani N, McCarthy MI, Hague S, Batty S, Conway GS, White D, Todd JA, Franks S, Williamson R. Linkage and association of insulin gene VNTR regulatory polymorphism with polycystic ovary syndrome. Lancet 1997; 349: 986-90 https://doi.org/10.1016/S0140-6736(96)08368-7
  7. Millan JL, Sancho J, Calvo RM, et al. Role of the pentanucleotide (tttta)_n polymorphism in the prom-oter of the $CYP11{\alpha}$ gene in the pathogenesis of hi-rsutism. Fertil Steril 2001; 75: 797-802 https://doi.org/10.1016/S0015-0282(01)01677-6
  8. Gaasenbeek M, Brenda LP, Ulla S, et al. Large-scale analysis of the relationship between CYP11a prom-otor variation, polycystic ovarian syndrome, and se-rum testoeterone. J Clin Endocrionol Metab 2004; 89: 2408-13 https://doi.org/10.1210/jc.2003-031640
  9. Lim SK, Kim MS, Lee SH, Baek KH. Polymorphism of CYP17 and $CYP11{\alpha}$ for polycystic ovary syn-drome in a Korean population. Korean J Genetics 2002; 24: 343-8
  10. Zheng W, Yu-Tang G, Xiao-Ou S, Wanqing W, Qiu-yin C, Qi D, Jeffrey SM. Population-based case-control study of CYP11A gene polymorphism and breast cancer risk. Cancer Epidemiol Biomarkers Prev 2004; 13(5): 709-14