癫痫患者ABCC2基因多态性与丙戊酸钠血药浓度、疗效的相关性分析

Correlation analysis between ABCC2 gene polymorphism with blood concentration of sodium valproate and efficacy in epileptic patients

目的:探究癫痫患者ATP结合盒式家族C成员2(ABCC2)基因多态性与丙戊酸钠血药浓度、药效的关系,为癫痫临床治疗提供参考。方法:收集佳木斯大学附属第一医院137例癫痫患者血液样本,高效液相色谱(HPLC)法检测丙戊酸钠血药浓度,限制性片段长度多态性-聚合酶链式反应检测ABCC2基因位点rs717620、rs3740066基因型,对比位点不同基因分型患者标准化血药浓度以及临床疗效差异。结果:rs717620、rs3740066存在单核苷酸多态性,均为野生型纯合子CC型、突变杂合子CT型、突变纯合子TT型。rs717620、rs3740066基因多态性基因型频率分布符合Hardy-weinberg定律。rs717620基因型CC型患者标准化血药浓度、血药剂量、临床有效率高于基因型CT、TT型以及CT+TT型(P <0. 05)。rs3740066基因型CC型患者标准化血药浓度、血药剂量、临床有效率高于基因型CT、TT型以及CT+TT型(P <0. 05)。结论:ABCC2基因rs717620、rs3740066位点基因多态性与丙戊酸钠血药浓度、临床疗效有关,此两处位点发生突变可能导致血药浓度降低、疗效下降。

Objective: To explore the relationships between the gene polymorphism of ATP-binding cassette-2( ABCC2) with the blood concentration of sodium valproate and pesticide effect in patients with epilepsy,in order to provide some reference for the clinical treatment of epilepsy. Methods: Blood samples of 137 epileptic patients in the First Affiliated Hospital of Jiamusi University were collected,the blood concentration of sodium valproate was determined by high performance liquid chromatography( HPLC),the ABCC2 loci rs717620 and rs3740066 genotypes were detected by restriction fragment length polymorphism-polymerase chain reaction,the differences of standardized blood concentration and clinical efficacy between different genotyping patients were compared.Results: There were single nucleotide polymorphisms in rs717620 and rs3740066,they were wild type homozygote CC type,mutant heterozygote CT type and mutant homozygous TT type. The frequency distributions of rs717620 and rs3740066 polymorphisms were consistent with Hardy-weinberg law. The standardized blood concentration,blood dose and clinical effective rate of rs717620 genotype CC patients were higher than those of genotype CT,TT and CT + TT patients( P < 0. 05). The standardized blood concentration,blood dose and clinical effective rate of rs3740066 genotype CC patients were higher than those of genotype CT,TT and CT + TT patients( P < 0. 05).Conclusion: The polymorphisms of ABCC2 gene rs717620 and rs3740066 loci are related to the serum concentration of sodium valproate and clinical efficacy. The mutation of rs717620 and rs3740066 loci can lead to the decrease of blood drug concentration and curative effect.