Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Pharmacogenetic Impact on Korean Patients Receiving Antiepileptic Drugs

항전간제를 투여받은 한국인 환자에서의 약리유전학적 영향

  • Kim, Jeong-Oh (Laboratory of Medical Oncology, Research Institutes of Medical Science, College of Medicine, Catholic University) ;
  • Lee, Han-Hee (Division of Medical Oncology, Department of Internal Medicine, College of Medicine, Catholic University) ;
  • Shin, Jung-Young (Laboratory of Medical Oncology, Research Institutes of Medical Science, College of Medicine, Catholic University) ;
  • Zhang, Xiang Hua (Laboratory of Medical Oncology, Research Institutes of Medical Science, College of Medicine, Catholic University) ;
  • Oh, Ji-Eun (Laboratory of Medical Oncology, Research Institutes of Medical Science, College of Medicine, Catholic University) ;
  • Kim, Yeong-In (Department of Neurology, College of Medicine, Catholic University) ;
  • Lee, Jeong-Hyun (Laboratory of Medical Oncology, Research Institutes of Medical Science, College of Medicine, Catholic University) ;
  • Kang, Jin-Hyoung (Division of Medical Oncology, Department of Internal Medicine, College of Medicine, Catholic University)
  • 김정오 (가톨릭대학교 의과대학 의과학연구원 종양내과 연구소) ;
  • 이한희 (가톨릭대학교 의과대학 내과학교실 종양내과) ;
  • 신정영 (가톨릭대학교 의과대학 의과학연구원 종양내과 연구소) ;
  • 장향화 (가톨릭대학교 의과대학 의과학연구원 종양내과 연구소) ;
  • 오지은 (가톨릭대학교 의과대학 의과학연구원 종양내과 연구소) ;
  • 김영인 (가톨릭대학교 의과대학 신경과학교실) ;
  • 이정현 (가톨릭대학교 의과대학 의과학연구원 종양내과 연구소) ;
  • 강진형 (가톨릭대학교 의과대학 내과학교실 종양내과)
  • Received : 2012.05.30
  • Accepted : 2012.08.16
  • Published : 2012.08.30
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Abstract

Epilepsy is the most prevalent chronic neurological disorder and can be controlled by antiepileptic drugs (AEDs) in up to 70% of patients. We performed an association study between adverse drug reactions and the genetic polymorphisms of CYP2C9, CYP2C19, ABCB1, and SCN1A. The clinical data of 83 epilepsy patients who had received AEDs containing carbamazepine (CBZ) were collected. We extracted genomic DNA from peripheral blood and then genotyped CYP2C9 ($CYP2C9^*2$, $CYP2C9^*3$), CYP2C19 ($CYP2C9^*2$, $CYP2C9^*3$), ABCB1 (C3435T), and SCN1A (IVS5N+5 G>A) using direct sequencing. The allele frequencies of $CYP2C9^*3$, $CYP2C9^*2$, $CYP2C9^*3$, ABCB1 (3435C>T), and SCN1A (IVS5N+5 G>A) were 0.93, 0.72, 0.91, 0.61, and 0.55, respectively. Statistically significant differences were indicated from the data obtained. Patients with SCN1A genotype CC or CT were compared with patients with SCN1A genotype TT while using more than 500mg of carbamazepine. We have associated functional polymorphisms with the dose used in regular clinical practice for Korean epilepsy patients who had received antiepileptic drugs (AEDs) containing carbamazepine. For AEDs, we found that one of the SCN1A genotypes is associated with a 500 mg dose. There was no association found with CNS ADR caused by AEDs.

간질은 가장 흔한 만성 신경 장애로 70% 이상의 환자에서 항전간제로 증상의 조절이 가능하다. 약물의 치료효과를 예측하는데 있어 개인이 가진 유전적 다형성이 부분적인 영향을 주는 것으로 알려지면서 항전간제의 효과에 영향을 주는 유전자 연구가 빠르게 진행되고 있다. 본 연구에서는 83명의 간질 환자를 대상으로 간질 환자의 약물대사와 관련된 것으로 알려진 유전자(CYP2C9, CYP2C19, ABCB1, SCN1A)의 다형성과 약물부작용의 관계에 대해 연구하였다. 연구 결과, 약물 이상 반응과 약물 용량의 상관관계는 통계적으로 유의한 수준은 관찰되지 않았다. 한편, carbamazepine 계열에서의 환자군에서는 SCN1A 유전자의 인트론 유전자 유전형 CC와 CT 유전형에 비해 TT 유전형에서 약물용량과 연관을 보였으며, 500 mg 이상의 용량을 투약한 환자에서는 TT 유전형에 비해 CC와 CT를 가진 유전형에서 통계적으로 유의한 상관성을 보였다.

Keywords

References

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