Association Study Between MVP, AQP4, KCNJ10Gene Polymorphisms,and Drug Resistance Of Partial Epilepsy In Chinese Han Population

Background and objective:Epilepsy is one of the most common clinical neurological diseases. Among all the epilepsy patients, about30%would not acquire complete control of seizures after treatment of adequate and reasonable chosen AEDs. These patients are expected to develop drug resistance to multiple AEDs, which would bring about heavy burdens to the patients and families. The major vault protein (MVP), aquaporin4(AQP4) and inward rectifier K+ion channel Kir4.1were found to be involved in the process of AEDs resistance in past researches. The pathogenesis of drug resistant epilepsy is considered to be multifactorial and still unclear. Recent studies suggested that the genetic single nucleotide polymorphisms (SNPs) may play a role in AEDs drug resistance in different ethnic groups from different regions. Based on this hypothesis, we here intend to explore the possible association between SNPs of MVP, AQP4, KCNJ10genes and drug resistance of partial epilepsy in Chinese Han population and provide new findings in regard to individual pharmacotherapy of epilepsy.Materials and methods:According to the criteria of epilepsy classification and definition of drug resistant epilepsy proposed by International League Against Epilepsy (ILAE). We recruited510partial epilepsy patients from epilepsy clinic, Neurology Department, Xiangya Hospital, Central South University.222of the epilepsy patients were classified into drug resistant group and288were classified into dug responsive group.206healthy people were matched as the control group. Details of epileptic medical history of patients were acquired at the clinic. All patients and healthy controls are Chinese Han population. The whole genome DNA was extracted from peripheral blood of each patients and healthy controls. The candidate SNP loci of MVP, AQP4and KCNJ10in Chinese han population were selected from the international Hapmap project database through Haploview software (version4.2). The Sequenom MassARRAY platform was used for genotyping of candidate SNP loci. The genotypic and allelic frequency, linkage disequilibrium (linkage disequilibrium, LD) and haplotypic frequency between the drug resistant group and drug responsive group of partial epilepsy as well as between the partial epilepsy patients and healthy controls were compared and analyzed.Results:1. in partial epilepsy patients, the drug resistant group had earlier onset age, more frequent seizures before medication and longer duration of epilepsy compared to drug resistant group (P<0.05); 2. for MVP SNPs, there is no significant difference in the genotypic and allelic frequency between drug resistant and responsive groups in partial epilepsy patients; there is no significant genotypic and allelic frequency difference between the partial epilepsy patients and healthy controls (P>0.05);3. for AQP4and KCNJ10SNPs, there is no significant difference in the genotypic and allelic frequency between drug resistant and responsive groups in partial epilepsy patients (P>0.05); KCNJ10rs1890532CG genotype frequency is higher in idiopathic partial epilepsy patients than in healthy controls (OR=0.636,95%CI (0.4090.989), P=0.045), but after Bofferoni’s method for multiple testing correction, there is no significant difference (P=0.405);4. in partial epilepsy patients, strong LD was detected between MVP rs12149746, rs1057451, rs9938630; AQP4rs1058424, rs3763043, rs35931and KCNJ10rs12122979, rs1186685, rs6690889(D’>0.7and r2>0.4), but there is no significant difference when comparing haplotypic difference between drug resistant and responsive groups (P>0.05).Conclusions:1. the early onset age, frequent seizures before medication and long duration of epilepsy may be measured as risk factors of drug resistance;2. SNPs of MVP gene may not be associated with drug resistance or seizure susceptibility of partial epilepsy in Chinese Han population; 3. SNPs of AQP4and KCNJ10gene may not be associated with drug resistance or seizure susceptibility of partial epilepsy in Chinese Han population;4. the haplotypes of MVP, AQP4and KCNJ10genes may not be associated with drug resistance of partial epilepsy in Chinese Han population.