目的探讨SCN1A基因的单核苷酸多态性(single nucleotide polymorphisms,SNP)与广西壮族癫痫患者卡马西平疗效的相关性。方法应用MassARRAY-IPLEX和基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)技术检测186例广西百色地区壮族卡马西平规范治疗的癫痫患者(有效组66例、无效组120例)外周血SCN1A基因rs3812718和rs1813502基因型,评估两组患者不同基因型和等位基因与卡马西平疗效的关联性,分析不同基因型间卡马西平血药浓度的差异。结果SCN1A基因rs3812718和rs1813502位点均检测到GG、GA和AA 3种基因型。与有效组相比,无效组rs3812718位点的等位基因分布(χ^2=17.810,P=0.000)和基因型分布(χ^2=17.873,P=0.000)的差异均有统计学意义;而rs1813502位点的等位基因分布(χ^2=1.606,P=0.206)和基因型分布(χ^2=1.546, P=0.462)的差异均无统计学意义;与GG +GA基因型相比,rs3812718位点的AA基因型显著降低卡马西平抗癫痫疗效(OR=3.776,95%CI:2.007-7.105)。在卡马西平治疗有效组,与GG+GA基因型比较,rs3812718位点AA基因型患者血药浓度(t=1.562,P=0.125)和rs1813502位点AA基因型患者血药浓度(t=0.843,P=0.562)的差异均无统计学意义。rs3812718和rs1813502没有强的连锁不平衡性。结论SCN1A基因rs3812718位点SNP可能与百色地区壮族癫痫卡马西平抵抗性形成有关。
Objective To assess the association of single nucleotide polymorphisms of SCN1A gene with therapeutic effect of carbamazepine among ethnic Zhuang Chinese patients with epilepsy. Methods Peripheral blood samples were taken from 186 epileptic patients (for whom 66 cases standard regime of carbamazepine treatment was effective. Genotypes of rs3812718 and rs1813502 loci of the SCN1A gene were determined by Mass ARRAY-IPLEX and matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Correlation between genotypes of patients and efficacy of carbamazepine treatment was analyzed. Results Three genotypes (GG, GA and AA) were detected at both rs3812718 and rs1813502 loci of the SCN1A gene. A significant difference was found in allelic distribution (χ^2=17.810, P=0.000) and genotypic distribution (χ^2=17.873, P =0.000) of the rs3812718 locus between the effective group and ineffective group. No such difference was found with the rs1813502 locus (χ^2=1.606, P=0.206;χ^2=1.546, P =0.462, respectively). Compared with the GG+ GA genotype, the AA genotype at rs3812718 locus significantly reduced the antiepileptic efficacy of carbamazepine (OR=3.776, 95%CI: 2.007-7.105). Among the 66 patients who were responsive to carbamazepine treatment, those with the AA genotype for rs3812718 or rs1813502 shown no significant difference in their blood concentration of carbamazepine compared with those with the GG+ GA genotype (t=1.562, P=0.125;t =0.843, P=0.562, respectively). rs3812718 and rs1813502 were not in strong linkage disequilibrium. Conclusion Polymorphisms of rs3812718 of the SCN1A gene is associated with carbamazepine resistance among ethnic Zhuang Chinese epilepsy patients from Baise region.
Chinese Journal of Medical Genetics
Single nucleotide polymorphism
Matrix-assisted laser desorption/ionization time of flight mass spectrometry