https://orcid.org/0000-0001-6094-1994
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.
Study Limitations
Lack of comparison with other experimental group including patients with nondrug-resistant epilepsy was the main study limitation that could be included in future studies. Another study limitation was the small sample size, which impeded further examination of the studied gene polymorphisms in relation to the clinical characteristics of the patients.
Data Sharing Statement
The datasets used and/or analyzed in this study are available from the corresponding author on reasonable request.
Author Contributions
Study concept and design: HNE-T, SA, AYN, THS, WMAF, SAA, AAS, AMT and MHH; clinical assessments and data collection: HNE-T, WMAF, and AMT; blood sampling and genetic assays: AAS, SAA and MHH; statistical analysis: AAS and MHH; literature research: HNE-T, SA, AYN, THS, WMAF, SAA, AAS, AMT and MHH; first manuscript drafting: MHH. All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors report no competing interests in this work.