Purpose

Gephyrin (GPHN) 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 CYP2C9 “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

GPHN 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, P<0.001. In addition, (TT+TC vs CC): OR 0.38, 95%CI: 0.18–0.77, P<0.001. Also, T vs C (OR 0.34, 95%CI: 0.22–0.51, P=<0.001). Similarly, CYP2C9 G>A polymorphism showed a significant increased risk of PRE (GG vs (GA+AA): OR 0.11, 95%CI: 0.05–0.23, P<0.001). Furthermore, (GG+GA vs AA): OR 0.18, 95%CI: 0.084–0.39, P<0.001. Also, G vs A (OR 0.24, 95%CI: 0.15–0.366, P=<0.001).

Conclusion

Mutation of both GPHN (rs928553) and CYP2C9 (rs1278237) genes may be implicated as a genetic mediators of resistance in patients with PRE.