Gene-Wide Tagging study of the Effects of Common Genetic Polymorphisms in the α Subunits of the GABA A Receptor on Epilepsy Treatment Response

Abstract

We aimed to identify the effect of SNPs in the α-subunits of GABAA receptors on epilepsy treatment outcomes by using a gene-wide tagging method. There were 720 epileptic patients included in the present study. A total of 136 tagging SNPs in GABRA1, GABRA2, GABRA3, GABRA4, GABRA5 and GABRA6 were genotyped by Illumina(®)GoldenGate(®) Genotyping platform. Clinical information, such as prescribed antiepileptic drugs, height, weight, epilepsy syndrome classification, etiology, number of attacks, renal function and liver function were collected. The associations between SNPs and epilepsy treatment outcomes were analyzed using SAS(®) version 9.1.3. Both multivariate logistic regression and multifactor dimensionality reduction analyses were performed. The results of single gene effects did not remain significant after Bonferroni's corrections. Further multivariate logistic regression and multifactor dimensionality reduction analyses of interactions between these genes showed that under adjustment of clinical factors, the epilepsy treatment outcomes were significantly associated with the genotype combinations of GABRA1 rs6883877, GABRA2 rs511310 and GABRA3 rs4828696 (p < 0.0001; adjusted r(2) = 0.149). Our results indicated that genetic variants in the α subunits of GABA(A) receptors may interactively affect the treatment responses of antiepileptic drugs. Further replication using an independent sample collection would be essential to confirm our findings.