ABCB1基因多态性与苯妥英钠治疗癫痫疗效的相关性研究  

Association study of ABCB1 genetic polymorphism and the effect of epilepsy with phenytoin treatment

作　　者：姜德华[1] 黄成琼[2] 王博[1] 孙飞[1] 吴世强[2] 

机构地区：[1]徐州市中心医院神经外科,江苏省221009 [2]徐州市中心医院药剂科,江苏省221009

出　　处：《中华临床医师杂志（电子版）》2015年第13期27-31,共5页Chinese Journal of Clinicians(Electronic Edition)

基　　金：徐州市科技局(XZZDY1306)

摘　　要：目的研究ATP结合盒B亚家族成员1转运蛋白(ABCB1)基因的遗传多态性对苯妥英钠治疗癫痫的影响。方法 200例癫痫患者按照患者临床资料分为控制组和耐药组,采集两组患者的外周血6 ml,依赖高效液相色谱法(HPLC)测定苯妥英钠血药浓度以及依靠PCR-RFLR法分析200例患者的ABCB1 C1236T、ABCB1 C3435T和ABCB1 G2677T/A三个单碱基突变位点。用SHEsis软件对ABCB1基因C1236T、C3435T和G2677T/A进行单体型推断,多组间统计数据比较采用单因素方差分析。结果在ABCB1 C1236T中CC基因型在耐药组的百分率为17.5%,显著高于控制组(2.1%),TT基因型在控制组百分率为55.4%,高于耐药组的百分率41.6%(P<0.05);在G2677T/A中GG基因型在耐药组分布达29.6%,高于控制组的9.7%,TT基因型在控制组的百分率为30.4%,高于耐药组(4.6%)(P<0.05);在C3435T位点,徐州地区癫痫患者耐药组和控制组的分布频率没有统计学差异(P=0.349)。单倍体检测发现TTC单体型在控制组中的分布频率较高为24.1%(P<0.05);没有观察到ABCB1基因多态性与苯巴比妥稳定血浆药物浓度存在相关影响。结论 ABCB1基因遗传多态性对苯妥英钠的血药浓度没有影响,但是影响苯妥英钠对癫痫患者的治疗效果。Objective To analyze the influence of ABCB1 geneticpolymorphisms on the efficacy of phenytoin （PHT） in epilepsy patients.Methods200 epilepsy patients who took PHT were divided into responsive group and pharmacoresistance group depending on clinical data of PHT treatment in epilepsy patients. The serum concentration of PTH was detected by high performance liquid chromatography （HPLC） method. ABCB1 polymorphisms were analyzed by the polymerase chain reaction restriction fragment length polymorphism （PCR-RFLP） method. Haplotypes were reconstructed to ABCB1 gene C1236T, C3435T and G2677T/A by SHEsis programs. One-Way analysis of variance was used for data analysis. ResultsIn ABCB1 C1236T, the rate of CC genotype in pharmacroresitance （17.5%） was higher than the responsive group （2.1%）, the rate of TT genotype in pharmacroresitance （41.6%） was lower than the responsive group （55.4%） （P〈0.05）; In ABCB1 G2677T/A, the rate of GG genotype in pharmacroresitance （29.6%） was higher than the responsive group （9.7%）, the rate of TT genotype in pharmacroresitance （4.6%） was lower than the responsive group （30.4%） （P〈0.05）; The rate of TTC haploid in pharmacroresitance （24.1%） was higher than the responsive group （8.8%） （P〈0.05）. The PTH serum concentration had no statistical significance in the patients with different genotype.ConclusionThere has no association between ABCB1 genetic polymorphism and PTH serum （PHTS） concentration, but the polymorphisms influence the efficacy of PTH in patients with epilepsy.

关 键 词：癫痫 ABCB1 苯妥英钠 单核苷酸多态性 

分 类 号：R742.1[医药卫生—神经病学与精神病学]