Gephyrin and CYP2C9 Genetic Polymorphisms in Patients with Pharmacoresistant Epilepsy

Hamdy N El-Tallawy; Sawsan Abuhamdah; Ahmed Y Nassar; Wafaa M A Farghaly; Tahia H Saleem; Sara A Atta; Ayat A Sayed; Amal M Tohamy; Mohammed H Hassan

doi:10.2147/PGPM.S327808

Gephyrin and CYP2C9 Genetic Polymorphisms in Patients with Pharmacoresistant Epilepsy

Pharmgenomics Pers Med. 2021 Sep 9:14:1133-1140. doi: 10.2147/PGPM.S327808. eCollection 2021.

Authors

Hamdy N El-Tallawy¹, Sawsan Abuhamdah^{2

3}, Ahmed Y Nassar⁴, Wafaa M A Farghaly¹, Tahia H Saleem⁴, Sara A Atta⁴, Ayat A Sayed⁴, Amal M Tohamy¹, Mohammed H Hassan⁵

Affiliations

¹ Department of Neurology and Psychiatry, Faculty of Medicine, Assiut University, Assiut, Egypt.
² Department of Pharmaceutical Sciences, College of Pharmacy, Al Ain University, Abu Dhabi, United Arab Emirates.
³ Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, University of Jordan, Amman, Jordan.
⁴ Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt.
⁵ Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, 83523, Egypt.

Abstract

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.

Keywords: pharmacoresistant epilepsy; real time-PCR; rs12782374G/A; rs928553T/C.

Grants and funding

The current research has been funded by Faculties of Medcine, Assiut and South Valley Universities, Egypt.