Pharmacogenetic study of phosphatase and tensin homolog polymorphism (rs701848) in childhood epilepsy: relation to circulating Wnt signaling.

Autor: Hassan MH; Department of Medical Biochemistry, Faculty of Medicine, South Valley University, Qena, Egypt., Nassar AY; Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt., Meki AMA; Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt.; Department of Biochemistry, Sphinx University, New Assiut city, Assiut, Egypt., Nasser SA; Department of Biochemistry, Faculty of Pharmacy, South Valley University, Qena, Egypt., Bakri AH; Department of Pediatrics, Faculty of Medicine, South Valley University, Qena, Egypt., Radwan E; Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt.; Department of Biochemistry, Sphinx University, New Assiut city, Assiut, Egypt.
Jazyk: angličtina
Zdroj: Neurological research [Neurol Res] 2024 Feb; Vol. 46 (2), pp. 99-110. Date of Electronic Publication: 2023 Sep 14.
DOI: 10.1080/01616412.2023.2257465
Abstrakt: Objective: The present study aimed at evaluating the potential contribution of Phosphatase and Tensin Homolog (PTEN) and its gene polymorphism (PTEN rs701848 T/C) in relation to Wingless/integrase-1 (Wnt) signaling in childhood epilepsy and the impact of antiepileptic medications on their serum levels.
Methods: This study included 100 children with epilepsy (50 pharmacoresistant and 50 pharmacoresponsive) and 50 matched controls. All subjects had their genotypes for the PTEN rs701848T/C polymorphism assessed using TaqMan TM assays and real-time PCR. By using the sandwich ELISA technique, the blood concentrations of PTEN and Wnt3a were measured.
Results: Serum Wnt3a levels in epileptic patients were significantly higher than in the control group, p  < 0.001. Children with epilepsy who received oxcarbazepine had considerably lower serum Wnt3a levels than those who didn't, p  < 0.001.With an AUC of 0.71, the cutoff value for diagnosing epilepsy as serum Wnt3a > 6.2 ng/mL has a sensitivity of 55% and a specificity of 80%. When compared to controls, epileptic children had considerably more (TT) genotype and less (TC and CC) genotypes, p  < 0.05 for all. Epileptic children had significantly higher (T) allele frequency than controls, p  = 0.006 with OR (95%CI) = 1.962(1.206-3.192). Pharmacoresistant epileptic children had significantly higher (TT) genotype compared to pharmacoresponsive type ( p  = 0.020).
Conclusion: We originally found a strong association between PTEN rs701848 T/C and childhood epilepsy, in particular pharmacoresistant type. Serum Wnt3a levels increased in epilepsy, but were not significantly different between different alleles of PTEN. In pharmaco-responsive children Wnt3a levels differed significantly between the different PTEN genotypes. Antiepileptics may affect Wnt3a levels.
Databáze: MEDLINE
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