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