Gephyrin and Genetic Polymorphisms in Patients with Pharmacoresistant Epilepsy.

Purpose: Gephyrin () is an essential protein in the regulation of inhibitory postsynaptic density and polymorphism in the corresponding gene may have a role in the development of pharmacoresistant epilepsy (PRE). For the first time, we aimed to evaluate the association of rs928553T/C variants with PRE susceptibility. Moreover, we have analyzed the genetic polymorphism affecting "rs12782374G/A" in the same population to detect the effect of SNP on the drug-metabolizing ability of patients with PRE.

Patients And Methods: This case-control study enrolled 100 patients (group A) and 100 healthy, age and sex-matched controls, unrelated to patients (group B). TaqMan™ assays using real-time PCR were run for genotyping of rs928553T/C and rs12782374G/A in all participants.

Results: T>C polymorphism revealed significant risk association with occurrence of PRE using dominant, recessive and codominant models as follows: TT vs (TC+CC): OR 0.23, 95%CI: 0.13-0.43, <0.001. In addition, (TT+TC vs CC): OR 0.38, 95%CI: 0.18-0.77, <0.001. Also, T vs C (OR 0.34, 95%CI: 0.22-0.51, =<0.001). Similarly, G>A polymorphism showed a significant increased risk of PRE (GG vs (GA+AA): OR 0.11, 95%CI: 0.05-0.23, <0.001). Furthermore, (GG+GA vs AA): OR 0.18, 95%CI: 0.084-0.39, <0.001. Also, G vs A (OR 0.24, 95%CI: 0.15-0.366, =<0.001).

Conclusion: Mutation of both (rs928553) and (rs1278237) genes may be implicated as a genetic mediators of resistance in patients with PRE.