SCN2A基因多态性与丙戊酸钠治疗壮族癫痫患者疗效的相关性

目的：研究SCN2A基因多态性与丙戊酸钠治疗壮族癫痫患者疗效的相关性。方法：收集224例广西百色地区丙戊酸钠（VPA）规范治疗的壮族癫痫患者（有效组85例，无效组139例）为研究对象，采用聚合酶链式反应-限制性片段长度多态性（polymerase chain reaction-restriction fragment length polymorphism，PCR-RFLP）技术和直接测序法检测患者外周血SCN2A位点rs17183814和rs1864885基因多态性，利用LC-MS色谱法测定VPA血药浓度，利用SHEsis软件对rs17183814和rs1864885进行连锁不平衡分析。结果：无效组与有效组相比，rs17183814位点等位基因分布（χ²=9.707，P=0.002）和基因型分布（χ²=11.202，P=0.004）的差异均有统计学意义，而rs1864885位点等位基因分布（χ²=0.792，P=0.374）和基因型分布（χ²=0.763，P=0.683）的差异均无统计学意义。与GG+GA基因型相比，rs17183814的AA基因型显著降低VPA疗效，OR值（95%可信之间）为2.925（1.373~6.233）。有效组中rs17183814的GG、GA和AA基因型患者VPA血药浓度差异（F=5.016，P=0.368）和rs1864885的AA、AG和GG基因型患者VPA血药浓度差异（F=3.215，P=0.102）均无统计学意义。rs17183814和rs1864885没有连锁不平衡性。结论：SCN2A基因位点rs17183814单核苷酸多态性可能与壮族癫痫丙戊酸钠抵抗性形成有关。

Association between SCN2A gene polymorphism and the efficacy of valproic acid sodium in the treatment of Zhuangzu epilepsies

OBJECTIVE To investigate the association between SCN2A gene polymorphism and the efficacy of valproic acid sodium in the treatment of Zhuangzu epilepsies.METHODS The 244 Zhuangzu epileptic patients (85 cases in effective group and 139 cases of ineffective group) treated with VPA in Baise, Guangxi were enrolled in this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing were used to detect rs17183814 and rs1864885 gene polymorphisms at SCN2A locus in peripheral blood. LC-MS was used to determine VPA plasma concentration. Linkage disequilibrium analysis was performed for rs17183814 and rs1864885 using SHEsis software.RESULTS Compared with the effective group, the differences in the allele distribution (χ²=9.707, P=0.002) and genotype distribution (χ²=11.202, P=0.004) of the rs17183814 loci in the ineffective group were statistically significant. There was no significant difference in allele distribution (χ²=0.792, P=0.374) and genotype (χ²=0.763, P=0.683) of rs1864885 locus. Compared with the AA +AG genotype, the rs17183814 AA genotype significantly reduced the efficacy of valproic acidsodium (OR=2.925, 95%CI:1.373-6.233). There were no significant differences in VPA blood concentration of genotype GG, GA and AA of rs17183814 loci in the ineffective group (F=5.016, P=0.368). There were no significant differences in VPA blood concentration of genotype AA, AG and GG of rs1864885 loci in the ineffective group (F=3.215, P=0.102). There was no linkage disequilibrium for rs17183814 and rs1864885.CONCLUSION The single nucleotide polymorphisms of rs17183814 in SCN2A gene may be associated with the formation of valproic acid sodium Zhuangzu resistant epilepsy.