Pharmacogenomics and Personalized Medicine (Sep 2021)

Gephyrin and CYP2C9 Genetic Polymorphisms in Patients with Pharmacoresistant Epilepsy

  • El-Tallawy HN,
  • Abuhamdah S,
  • Nassar AY,
  • Farghaly WMA,
  • Saleem TH,
  • Atta SA,
  • Sayed AA,
  • Tohamy AM,
  • Hassan MH

Journal volume & issue
Vol. Volume 14
pp. 1133 – 1140

Abstract

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Hamdy N El-Tallawy,1 Sawsan Abuhamdah,2,3 Ahmed Y Nassar,4 Wafaa MA Farghaly,1 Tahia H Saleem,4 Sara A Atta,4 Ayat A Sayed,4 Amal M Tohamy,1 Mohammed H Hassan5 1Department of Neurology and Psychiatry, Faculty of Medicine, Assiut University, Assiut, Egypt; 2Department of Pharmaceutical Sciences, College of Pharmacy, Al Ain University, Abu Dhabi, United Arab Emirates; 3Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, University of Jordan, Amman, Jordan; 4Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt; 5Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, 83523, EgyptCorrespondence: Mohammed H Hassan Email [email protected]: 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, PA 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, rs928553T/C, rs12782374G/A, real time-PCR

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