论文部分内容阅读
目的探讨卡马西平(CBZ)药物代谢个体差异性的遗传学机制,从而指导临床抗癫痫治疗中的个体化用药。方法选取确诊为癫痫并适用CBZ的患者58例。首先利用PCR技术扩增患者外周血中包含等位基因CYP3A5*3(rs776746)的基因片段;其次采用基因测序法确定该等位基因各基因型的分布,将包含原始碱基(A)的基因序列归为A组,而将只含有突变碱基(C)的基因序列归为B组;最后,应用高效液相色谱法测定两组患者外周血中CBZ及其代谢产物10,11-环氧化卡马西平(CBZE)的血药浓度。采用t检验,比较A、B两组患者CBZ和CBZE血药浓度的差异。结果 A组患者CBZ的浓度明显低于B组(P<0.01);A组患者CBZE的浓度明显高于B组(P<0.05)。CYP3A5*3的基因多态性与CBZ及其代谢产物CBZE的血药浓度相关,CYP3A5*3突变纯合型CBZ代谢减慢,血药浓度相应增高,应给予相对小剂量的CBZ,以提高临床用药的安全性。结论 CYP3A5*3的基因多态性可能作为临床治疗中CBZ剂量个体化的一项重要参考依据。
Objective To investigate the genetic mechanism of individual differences in carbamazepine (CBZ) drug metabolism and to guide the individualized use of anti-epileptic drugs in clinical practice. Methods Fifty-eight patients with epilepsy and CBZ were selected. Firstly, the gene fragment of allele CYP3A5 * 3 (rs776746) in peripheral blood of patients was amplified by PCR. Secondly, the genotype distribution of the allele was determined by gene sequencing. The gene containing the original base (A) The sequence was classified as group A, while the gene sequence containing only mutant base (C) was classified as group B. Finally, high performance liquid chromatography (HPLC) was used to determine the CBZ and its metabolites Plasma concentrations of carbamazepine (CBZE). T test was used to compare the blood concentration of CBZ and CBZE in patients with A and B groups. Results The concentration of CBZ in group A was significantly lower than that in group B (P <0.01). The concentration of CBZE in group A was significantly higher than that in group B (P <0.05). CYP3A5 * 3 gene polymorphism and CBZ and its metabolites CBZE plasma concentration related to CYP3A5 * 3 mutant homozygous CBZ metabolism slowed down, the corresponding increase in plasma concentration should be given a relatively small dose of CBZ to improve the clinical Medication safety. Conclusion CYP3A5 * 3 gene polymorphism may be an important reference for the individualization of CBZ dose in clinical treatment.