Common variants of ATP1A3 but not ATP1A2 are associated with Chinese genetic generalized epilepsies

• This study included 484 Chinese genetic generalized epilepsy patients.
• ATP1A3 rs8107107 is associated with genetic generalized epilepsies.
• Common variants of ATP1A2 are not associated with genetic generalized epilepsies.

ObjectiveATP1A2 and ATP1A3 are genes that code for catalytic subunits of Na/K-ATPases, which play important roles in the basal electrophysiological states of nerve cells. The aim of this study was to investigate whether genetic polymorphisms of ATP1A2 and ATP1A3 influence susceptibility to genetic generalized epilepsies (GGEs) and the efficacy of anti-epileptic drugs in a Chinese population.MethodSix ATP1A2 tagged single-nucleotide polymorphisms (tagSNPs) and two ATP1A3 tagSNPs were were genotyped by allele-specific MALDI–TOF mass spectrometry in 484 Chinese GGE patients (280 drug-responsive and 204 drug-resistant patients) and 284 healthy controls.ResultsSignificant differences were found in the frequencies of the ATP1A3 rs8107107 C allele and the CC genotype between the GGEs and the healthy controls (11% vs. 15%, odds ratio (OR) = 0.807 (0.68–0.960), p = 0.021 and 0.4% vs. 3.2%, OR = 0.121 (0.026–0.565), p = 0.002, respectively). The frequency of the rs8107107 CT + CC genotype was significantly lower among the GGE patients than among the healthy controls (15% vs. 26.8%, OR = 0.327 (0.248–0.942), p = 0.001). No significant differences in the frequencies of six ATP1A2 tagSNPs or ATP1A2 haplotypes were found between the GGEs and the healthy controls. No tagSNPs were involved in anti-epileptic drug resistance.ConclusionOur findings demonstrated that common variants of ATP1A3 but not ATP1A2 were associated with the susceptibility to GGEs in a Chinese population, which indicates that the ATP1A3 gene plays a significant role in the pathophysiology of genetic generalized epilepsies.