Combined effect between two functional polymorphisms of SLC6A12 gene is associated with temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is the most common epilepsy subtype with complex genetic structure. A recent study in four populations (Ireland, UK, Australia and Finland) reported an allelic association between betaine/GABA transporter-1 (BGT-1 or SLC6A12) and mesial temporal lobe epilepsy with hippocampal sclerosis. To demonstrate the association between SLC6A12 gene polymorphisms and TLE, TaqMan method was used to genotype five single-nucleotide polymorphisms of SLC6A12 gene in 358 TLE patients and 596 nonepileptic control subjects of Chinese Han origin. Real-time PCR was used to detect the effects of variations on gene expression associated with TLE. Though, the single-marker analysis did not demonstrate allelic association with TLE, rs542736–rs557881 interaction showed significant association. The SLC6A12 expression levels in peripheral blood mononuclear cells were significantly higher in TLE patients than in control subjects and were correlated to rs542736 G–rs557881 A haplotypes. Our preliminary results suggested combined effect of two common polymorphisms on SLC6A12 gene may be associated with TLE, but the precise mechanism needs further investigation.