中国人群难治性癫痫患者CYP2C19*2基因型对癫痫耐药的影响

INFLUENCE OF CYP2C19*2 GENOTYPES ON ANTI-EPILEPTIC DRUG RESISTANCE OF REFRACTORY EPILEPTICS IN CHINA

目的:研究中国人群难治性癫痫患者CYP2C19*2基因型对癫痫耐药的影响,促进阐明难治性癫痫的耐药机制。方法:采用聚合酶链反应(PCR)-限制性片段长度多态性(RFLP)方法对难治性癫痫患者(接受癫痫治痫灶切除的患者)和非难治性癫痫患者(单药有效的癫痫患者)的CYP2C19*2(681G→A)位点进行基因型分析,对患者杂合型和纯突变型的样本进行抽样测序验证,以确保基因分型结果准确。对两组基因和基因型频率采用卡方检验的统计学分析,选用SPSS12.0版软件进行处理。结果:收集了96例难治性癫痫患者和305例非难治性癫痫患者。CYP2C19*2等位基因频率:难治组G64.6%,A35.4%;非难治组:G67.9%,A32.1%;难治组突变基因频率高于非难治组但没有统计学差异(P>0.05)。CYP2C19*2基因型频率:难治组GG33.3%,GA62.5%,AA4.2%;非难治组GG44.6%,GA46.6%,AA8.9%。难治组和非难治组基因型频率具有统计学差异(P<0.05),难治组中GG型频率显著低于非难治组,GA型频率高于非难治组(P<0.05);而AA型频率在两组内虽然不同却没有统计学差异。另外,进行基因型组合后,只有无突变(GG)与突变(GA和AA)基因型频率在两组间有统计学差异(P<0.05),难治组突变基因型频率高于非难治性组(66.7%:55.4%)。结论:中国人群难治性癫痫患者与非难治性癫痫患者的CYP2C19*2基因型分布频率有统计学差异,难治性癫痫组CYP2C19*2突变基因型频率高于非难治组;癫痫耐药与CYP2C19*2基因型之间没有关联性,阐明癫痫耐药机制应更加关注多基因之间的联合作用尤其是影响脑组织局部药物浓度的基因。

Objective：To investigate the relationship between CYP2C19＊2 genotypes and medically refractory epilepsy in China in order to explore drug resistance mechanisms.Methods：Patients with medically refractory epilepsy having received surgical treatment using resection of epileptogenic focus and patients with medically non-refractory epilepsy responsive to monotherapy of AEDS were collected in the study.CYP2C19＊2（681G→A）genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP）method,and the method was further validated by sequencing method.The frequency of genotypes and alleles between the two groups was compared by Chi-square test.Results：Ninety six refractory epileptics and 305 non-refractory epileptics were collected.The CYP2C19＊2 allelic frequency：refractory epileptics group：G 64.6%,A 35.4%;non-refractory group：G 67.9%,A 32.1%;mutant allele A in the refractory epileptics group was higher than that in the non-refractory epileptics group but had no significant difference（P〉0.05）.The CYP2C19＊2 genotypes had significant difference between the two groups（P〈0.05）,GG type in the refractory epileptics group was significantly lower than that in the non-refractory epileptics group,conversely,GA type was significantly higher（P〈0.05）,and AA type had no significant difference.When genotypes were combined,only the wild type（GG）and types containing mutant allele A（GA＋AA）had significant difference between the two groups（P≤0.05）;types containing mutant allele A in the refractory epileptics group was significantly higher than that in the non-refractory epileptics group（66.7% to 55.4%）.Conclusion：The CYP2C19＊2 genotypes are significantly different between refractory epileptics and non-refractory epileptics.The genotypes containing mutant allele A in the refractory epileptics are significant higher than those in the non-refractory epileptics,which indicates that CYP2C19＊2 genotypes have no relevance to drug resistance of medically refractory epilepsy.