Association Study Between The Polymorphism Of SLC6A11and APOE Gene And Drug-resistant Epilepsy In Han Chinese

Background:Epilepsy is one of the most common and serious chronic neurological diseases in human. Antiepileptic drugs (AEDs) is the main approach to the control of epileptic seizures. Although great progress has been made in drug treatment of epilepsy, but there are still about30%of epilepsy patients resistant to antiepileptic drugs. Drug-resistant epilepsy has become a big problem of public health, the mortality rate of drug-resistant epilepsy is4to7times higher than common epilepsy.GABA is one of the main inhibitory neurotransmitters in the central nervous system, plays a key role in mediation of the neural network excitatory and is closely related to epilepsy development. GABA transporter is a glycoprotein mainly located in neurons and glial cell membrane, participate in the transportation and release process of GABA in the central nervous system. A study in Korean found positive correlations between the SLC6A11rs2272400and drug resistant epilepsy. But there is no relevant reports about the correlations between the SLC6Alland drug resistant epilepsy in Chinese Han population. Apo lipoprotein E (APOE) is an important lipid transport molecules in central nervous system, plays a key role in axonal growth, synapse formation, impaired nerve tissue repair. Studies showed that APOE polymorphism was probably associated with drug resistant temporal lobe epilepsy. However, whether APOE polymorphism is associated with all types of drug resistant epilepsy is still unknown. So it is necessary to study the relationship between SLC6A11and APOE gene polymorphism and drug-resistant epilepsy in Chinese Han population.Objective:To investigate the association between the SLC6A11and APOE polymorphism and drug resistant epilepsy.Material and Methods:A population-based case-control design was applied in our study.1. The study consisted of480outpatients diagnosed with epilepsy who visited the Xiangya hospital central-south university from August2010to October2012.273patients were recruited in drug-responsive group and207patients were recruited in drug-resistant group.2. Genomic DNA was extracted from peripheral blood leukocytes of each subject by Phenol Chloroform Method.3.16Tag single nucleotide polymorphisms (tagSNP) in SLC6A11and APOE gene were selected through hapmap and National Center for Biotechnology Information (NCBI) databases. All the tagSNP were genotyped by VeraCode GoldenGate Genotyping Assay system and the data were analyzed by SPSS21. 4. To analysis the genotype frequency distribution of the control group whether meets Hardy-Weinberg equilibrium by Goodness-of-fit Chi-square test.5. All the data of15tagSNP were analyzed by the association study.Results:1. We detected16tagSNPs of SLC6A11and APOE genes, one SNPs which belongs to SLC6A11are not suitable for the gene chip detection for clusting caused by chromosome structural variation.2. The total15SNPs distribution in the population of patients with epilepsy accord with Hardy-Weinberg equilibrium3. Genotypes and alleles distributions in the13SNPs of SLC6A11showed no statistically difference between the drug-responsive and drug-resistant groups (P>0.05). Strong linkage was found between rs2304725and rs1881354. There is no statistically significant difference haplotype between the drug-responsive and drug-resistant groups (P>0.05).4. Genotypes and alleles distributions in the2SNPs of APOE showed no statistically difference between the drug-responsive and drug-resistant groups(P>0.05).Conclusion:1. The13SNPs of SLC6A11gene may not be related to drug-resistant epilepsy in Chinese Han population. 2. The2SNPs of APOE gene may not be related to drug-resistant epilepsy in Chinese Han population.3. Strong linkage was found between rs2304725and rs1881354in SLC6A11gene.