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.

Objectives: Acute kidney injury (AKI) is a critical clinical event characterized by a reduction in the excretory function of the kidneys. N-acetylcysteine (NAC), N-acetylmethionine (NAM) and N-acetylglucosamine (NAG) are antioxidants with scanty known genetic mechanisms. We aimed to assess both kidney injury molecule-1 (KIM-1) and growth-arrested DNA damage-inducible gene-153 (GADD-153) genes expression in paracetamol (PA) induced AKI. Also, to recognize whether NAC, NAM and/or NAG have roles in altering the expression of these genes for ameliorating the AKI induced by PA. Methods: The present preliminary study achieved the AKI model by oral administration of PA therapeutic dose for 15 days in experimental male rats. Serum urea, creatinine, and renal oxidative stress parameters were analyzed. Genetic expression of KIM-1 and GADD-153 were determined using real time-PCR. Results: Significant elevations of serum urea, creatinine and nitric oxide in renal tissue after PA administration; however, total thiol content was reduced. In addition, both KIM-1 and GADD-153 were upregulated. These biochemical alterations were improved after using NAC and partially after NAM; however, NAG had little effect. Conclusions: Up-regulation of both KIM-1 and GADD-153 occur in AKI induced by PA, which was significantly reversed by NAC.