癫痫患者药物基因多态性与拉莫三嗪血药浓度的相关性研究

发布时间：2018-01-26 01:21

本文关键词： 癫痫拉莫三嗪基因多态性血药浓度药代动力学　出处：《浙江大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的研究癫痫患者OCT1、ABCG2、ABCC2和HNF4a基因多态性对拉莫三嗪血药浓度及疗效的影响。方法本研究纳入在浙江大学医学院附属第二医院神经内科接受拉莫三嗪单药治疗的癫痫患者共112例,记录每位患者的拉莫三嗪药物剂量,收集他们的血标本并根据药物剂量、体重计算标准化拉莫三嗪血药浓度,随访观察疗效至少1年时间。应用PCR扩增测序法对OCT1 rs2282143、rs628031, ABCG2 rs2231142、rs2231137, ABCC2 rs2273697和HNF4α rs2071197、rs3212183作基因型分析,并评估拉莫三嗪治疗1年的疗效。采用SPSS20.0软件统计各基因型分布频率,分析基因多态性与拉莫三嗪剂量、血药浓度及疗效间的相关性。结果OCT1 rs2282143、rs628031, ABCG2 rs2231142、rs2231137, ABCC2 rs2273697和HNF4a rs2071197、rs3212183的基因型频率均符合哈迪-温伯格定律分布。OCT1 rs628031和ABCG2 rs2231142基因多态性与标准化拉莫三嗪血药浓度具有相关性(P0.05),反之,OCT1 rs2282143、ABCG2 rs2231137、ABCC2 rs2273697和HNF4a rs2071197、rs3212183基因多态性对拉莫三嗪血药浓度无明显作用。OCT1、ABCG2、ABCC2和HNF4α基因多态性与拉莫三嗪疗效问无显著关联。结论OCT1 rs628031和ABCG2 rs2231142基因多态性与癫痫患者拉莫三嗪的药代动力学具有显著相关性,未来的基因型筛查可为临床实践的个体化诊疗提供参考。
[Abstract]:Objective to study the ABCG2 of OCT1 in epileptic patients. Effects of ABCC2 and HNF4a gene polymorphisms on serum concentration and efficacy of lamotrigine. Methods the study was conducted in the Department of Neurology, second affiliated Hospital of Zhejiang University Medical College. There were 112 patients. The doses of lamotrigine were recorded for each patient, their blood samples were collected and standardized lamotriazine concentrations were calculated based on the drug dose and body weight. OCT1 rs2282143rs628031, ABCG2 rs2231142 were detected by PCR amplification sequencing. The genotypes of rs2231137, ABCC2 rs2273697 and HNF4 伪 rs2071197 rs3212183 were analyzed. To evaluate the efficacy of lamotrigine for one year, SPSS20.0 software was used to calculate the frequency of genotypes, to analyze the gene polymorphism and the dose of lamotrigine. Results OCT1 rs2282143rs628031, ABCG2 rs2231142, rs2231137. ABCC2 rs2273697 and HNF4a rs2071197. Genotypic frequencies of rs3212183 in accordance with Hardy Weinberg's law distribution. OCT1 rs628031 and ABCG2. The polymorphism of rs2231142 gene was associated with the standardized serum concentration of lamotriazine. P0.05). On the contrary, OCT1 rs2282143n ABCG2 rs2231137 ABCC2 rs2273697 and HNF4a rs2071197. The polymorphism of rs3212183 gene had no effect on the serum concentration of lamotrigine. ABCC2 and HNF4 伪 gene polymorphisms were not significantly associated with the efficacy of lamotriazine. Conclusion OCT1 rs628031 and ABCG2. The polymorphism of rs2231142 gene was significantly associated with the pharmacokinetics of lamotrigine in epileptic patients. Future genotypic screening may provide a reference for individualized diagnosis and treatment in clinical practice.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R742.1

【相似文献】