Association of single nucleotide polymorphisms of SCN1A gene with therapeutic effect of carbamazepine among ethnic Zhuang Chinese patients with epilepsy

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 (χ2=17.810, P=0.000) and genotypic distribution (χ2=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 (χ2=1.606, P=0.206; χ2=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. Key words: Epilepsy; SCN1A gene; Single nucleotide polymorphism; Matrix-assisted laser desorption/ionization time of flight mass spectrometry