多药耐药基因多态性及其表达物与抗癫痫药疗效的相关性研究

目的研究癫痫患者外周血中多药耐药基因(MDR1)C3435T位点基因多态性及其表达物与患者血药浓度及疗效的相关性。方法选取服用卡马西平的癫痫患者49例,根据疗效分为有效组(NIE组)26例和耐药组(IE组)23例,测定其血药浓度;采用聚合酶链反应—限制性片段长度多态性分析(PCR-RFLP)技术检测MDR1C3435T位点的基因型;用流式细胞仪检测MDR1的表达物P-糖蛋白(Pgp)的表达。比较NIE组、IE组的CBZ血药浓度、Pgp的表达、MDR1 C3435T基因型。另纳入健康查体者28例为健康对照组。结果 IE组血清Pgp(3.6%±0.3%)明显高于NIE组(2.6%±0.5%)和健康对照组(2.3%±0.4%),差异有统计学意义(P<0.05);而IE组及NIE组基因型及CBZ血药浓度的差异却无统计学意义(P>0.05)。结论 MDR1 C3435T基因多态性与抗癫痫药CBZ的血药浓度及疗效没有显著相关性。

The relationship between genetic polymorphism and expressed matter of MDR1 gene with efficacy of carbamazepine

Objective To investigate the genotypes and expressed matter of C3435T of MDR1 in peripheral blood of patients with epilepsy,and to analyze the relationship between the genetic polymorphism of MDR1 gene with the efficacy of carbamzepine (CBZ).Methods Forth-nine epilepsy patients who took CBZ were enrolled,according to the blood concentration of CBZ and observation of efficacy,the patients were divided into intractable epilepsy group(IE group,23 cases ) and non intractable group(NIE group,26 cases).The C3435T polymorphism was analyzed by the polymerase chain reaction restriction fragment length polymorphism(PCR RFLP) method.The expression of serum Pgp was detected with flow cytometer.The blood concentration of CBZ and genotypes in IE group and NIE group was compared.28 healthy volunteer was enrolled as control group.Results The expression of serum Pgp in the IE group(3.6%±0.3%) was obviously higher than that in NIE group(2.6%±0.5%) and healthy control group(2.3%±0.4%),and the difference was statistical significance(P<0.05).The differences of genotypes in the both groups were not statistical significance(P>0.05).Conclusion No relationship was proved between the 3435T genetic polymorphism of MDR1 gene and the efficacy of CBZ in patients with epilepsy.