Abstracts

Rationale: Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the brain. GABAergic neurotransmission is terminated by the uptake of GABA into the presynaptic terminal and the surrounding astroglial cells by sodium-dependent transporters, such as GAT3. Therefore, the overexpression of GAT3 in the brain may cause neuronal hyperexcitability, a principal mechanism of epileptogenesis. We aimed to elucidate whether the genetic variations in the gene encoding GAT3 are associated with epileptogenesis. Methods: Five polymorphisms in coding region (cSNPs) of the GAT3 gene were genotyped for 400 patients with epilepsy and 207 controls using direct sequencing and real-time PCR, and the distribution of cSNPs was compared. Results: The homozygous mutant allele (CC) of cSNP-GAT3E5 was distributed significantly higher in control (27.5%) than in patient group (18.3%) (p=0.009, Fisher’s exact test). The relative risk (odds ratio) for susceptibility to epilepsy was 1.702 (95%CI=1.145-2.531, p=0.009) in individuals carrying homozygous wild-type (TT) or heterozygous allele (CT) compared with individuals carrying CC. Conclusions: The mutant allele (C) of cSNP-GAT3E5 may exert a protective effect against epileptogenesis in the manner which follows a pattern of autosomal recessive inheritance. Further study for elucidating the functional value of the mutant allele is needed.