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CYP2C19基因多态性对癫痫患者丙戊酸血药浓度的影响 被引量:23

Effects of CYP2C19 gene polymorphism on plasma concentration of valproic acid in patients with epilepsy
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摘要 目的:研究癫痫患者CYP2C19基因多态性与丙戊酸稳态血药浓度的关系。方法:运用PCR-RFLP方法对99例癫痫病人的CYP2C19*2(681G→A)和CYP2C19*3(636G→A)位点进行基因型分析,选择其中临床资料较全的88名,对其丙戊酸血药浓度检测结果与基因型结果进行统计学分析。结果:在99例患者中,同时分析两个位点共5种双位点基因型组合:681GG-636GG、681GA-636GG、681GG-636GA、681AA-636GG和681GA-636GA,分布频率为37.4%、42.4%、6.1%、9.1%和5.1%。其中681AA-636GG基因型患者的丙戊酸血药浓度与体重剂量的比值明显高于野生基因型(681GG-636GG)(P<0.05),其他基因型与野生型相比无统计学差异。结论:本研究结果证实CYP2C19基因多态性影响了丙戊酸血药浓度,说明药物遗传学研究对丙戊酸临床合理用药有指导意义。 To determine the effect of CYP2C19 gene polymorphism on plasma concentration at steady state (Css) of valproic acid (VPA) in patients with epilepsy. METHODS: CYP2C19 variants ( *2 and *3) in 99 patients were detected using PCR-RFLP method, and 88 of them were fttrther studied to determine the relationship between CYP2C19 polymorphism and plasma concentration of VPA. RESULTS: Studying on the *2 and *3, we found that there were five genotypes of CYP2C19 gene in these subjects, and that their frequencies were: 37.4% for 681GG-636GG, 42.4% for681GA-636GG, 6.1% for 681GG-636GA, 9.1% for 681AA-636GG and 5.1% for 681GA-636GA. The ratio of VPA plasma concentration to dosage was significantly higher in poor metabolizer (681AA-636GG) than in extensive metabolizer ( 681GG-636GG). CONCLUSION: The data suggest that CYP2C19 polymorphism significantly impacts the metabolism of VPA. The pharmacogenomics is important to rationalize the medication of VPA.
出处 《中国临床药理学与治疗学》 CAS CSCD 2007年第6期700-704,共5页 Chinese Journal of Clinical Pharmacology and Therapeutics
关键词 药物遗传学 CYP2C19 丙戊酸 癫痫 PCR-RFLP pharmacogenomics CYP2C19 valproicacid epilepsia PCR-RFLP
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参考文献8

  • 1Weber WW.The legacy of pharmacogenetics and potential applications[J].Mutat Res,2001;479:1-18. 被引量:1
  • 2王育琴,齐晓涟,黄越,陈彪.丙戊酸药物浓度与 CYP2C19 基因多态性关系的研究[J].中国医院药学杂志,2003,23(11):670-673. 被引量:28
  • 3De Morais SM,Wilkinson GR,Blaisdell J,et al.Identification of new genetic defect responsible for the polymorphism of (S) mephenytoin metabolism in Japanese[J].Mol Pharmacol,1994;46:594-598. 被引量:1
  • 4De Morais SM,Wilkinson GR,Blaisdell J,et al.The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans[J].J Biol Chem,1994;269:15419-15422. 被引量:1
  • 5Ohkubo Y,Ueta A,Ando N,et al.Novel mutations in the cytochrome P450 2C19 gene:a pitfall of the PCR-RFLP method for identifying a common mutation[J].J Hum Genet,2006;51:118-123. 被引量:1
  • 6Von Ahsen N,Richter M,Grupp C,et al.No influence of the MDR-1 C3435T polymorphism or a CYP3A4 promoter polymorphism(CYP3A4-V allele) on dose-adjusted cyclosporin A trough concentrations or rejection incidence in stable renal transplant recipients[J].Clin Chem,2001;47:1048-1052. 被引量:1
  • 7Kiang TK,Ho PC,Anari MR,et al.Contribution of CYP2C9,CYP2A6,and CYP2B6 to valproic acid metabolism in hepatic microsomes from individuals with the CYP2C9*1/*1 genotype[J].Toxicol Sci,2006;94:261-271. 被引量:1
  • 8Takakubo F,Kuwano A,Kondo Ⅰ.Evidence that poor metabolizers of (S) mephenytoin could be identified by haplotypes of CYP2C19 in Japanese[J].Pharmacogenetics,1996;6:265-267. 被引量:1

二级参考文献4

  • 1国家药典委员会编.中国药典2000年版临床用药须知 第3版[M].北京:化学工业出版社,2001.74. 被引量:1
  • 2De Morais S, Wilkinmn GR, Blaisdell J. et al. The major genetic defect responsible for the polymorphism of S - mephenytoin metabolism in humans [J]. J Biol Chem, 1994, 269(22): 15419-15422. 被引量:1
  • 3Kunihiko IT, Kazuyuki IN, Hiroshi NK, et al. Polymerase Chain Reaction-Single-Strand conformation po|ymorphism based determination of two major genetic defects responsible for a phenotypic polymorphism of cytochrome P450 (CYP) 2C19 in the japanese population[J ]. Analytical Biochemistry, 2000, 284( 1 ) :160. 被引量:1
  • 4Kristensen VN, Kelefiotis D, Kristensen T, et al. High-throughput methods for detection of genetic variation[J]. Biotechniques 2001,30(2) :318,324,326. 被引量:1

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