Association of GABRA6 1519 T>C (rs3219151) and Synapsin II (rs37733634) gene polymorphisms with the development of idiopathic generalized epilepsy

• Evaluated association of GABRA6 T>C and Syn II A>G gene variants with IGE.
• A significant association of these gene variants with IGE was observed.
• Significant interaction between these genes was observed.

SummaryThe idiopathic generalized epilepsy (IGE) is a neurological disorder which accounts for approximately 30% of all epilepsy cases. Patients identified with IGE syndromes have pharmacoresponsive epilepsies without abnormal neurological symptoms, structural brain lesions and are of unknown origin. A genetic etiology to IGEs has been proposed. Gamma amino butyric acid (GABA), a major inhibitory neurotransmitter acts by binding to transmembrane GABAA and GABAB receptors of both pre- and postsynaptic neurons. Synapsin II (SynII), a neuron specific phosphoprotein plays a major role in synaptogenesis and neurotransmitter release. The present study was carried out with an aim to evaluate the association of GABRA6 (rs3219151) T>C and Syn II (rs37733634) A>G gene polymorphisms with IGE. Molecular analysis revealed that the frequency of ‘CC’ genotype and ‘C’allele of GABRA6 (rs3219151) T>C gene polymorphism was significantly higher in IGE patients compared to healthy controls [CC vs. TT, χ2 = 26; p < 0.001; Odds ratio = 3.6 (95% CI; 2.1–5.9); C vs T, χ2 = 24.7; p < 0.001; Odds ratio = 1.78 (95% CI; 1.4–2.2)]. The frequency of ‘GG’ genotype and ‘G’ allele of the intronic polymorphism A>G in Syn II gene was also found to be significantly associated with the disease when compared to controls [GG vs AA, χ2 = 64.52; p < 0.001; Odds ratio = 7.37 (95% CI; 4.4–12.3); G vs. A, χ2 = 65.78; p < 0.001; Odds ratio = 2.57 (95% CI; 2.0–3.2)]. The generalized multifactor dimensionality reduction method was employed to detect gene–gene interactions. The gene–gene interaction at two loci involving GABRA6 and Syn II revealed a significant association [χ2 = 36.6, p < 0.001, Odds ratio = 3.17 (95% CI; 2.2–4.6)] with IGE. Therefore, the present study clearly indicates that both GABRA6 (rs3219151) T>C and Syn II (rs37733634) A>G polymorphisms are important risk factors for the development of IGE in the South Indian population from Andhra Pradesh. The gene–gene interaction studies demonstrated significant interactive effects of these two loci in the development of the disease.