Association of the APP rs463946 Polymorphism with Epilepsy Risk: A Case-Control Study from Georgia

Authors

DOI:

https://doi.org/10.66636/gmj.v1.i2.a110

Keywords:

Epilepsy, Amyloid beta-Protein Precursor, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Case-Control Studies, Georgia (Republic)

Abstract

Background  Epilepsy affects approximately 52 million people worldwide and genetic susceptibility plays an important role in epileptogenesis, yet evidence from Caucasus populations remains limited. The amyloid precursor protein (APP) gene is increasingly investigated for its role in neuronal excitability and neurodegeneration. This study evaluated the association between the APP rs463946 polymorphism and epilepsy risk in a Georgian cohort.

Methods  In this hospital-based case-control study, 57 adult patients with epilepsy and 50 age- and sex-matched healthy controls were recruited between 1 February and 20 October 2025. Genotyping of rs463946 (C>G) was performed using a TaqMan allelic discrimination assay. Associations were evaluated using chi-square tests and multivariable logistic regression adjusted for age and sex; risk estimates are expressed as odds ratios (ORs) with 95% confidence intervals (CIs). A two-sided p-value < 0.05 defined statistical significance.

Results  Genotype distribution differed significantly between patients and controls (χ² = 6.41; p = 0.041). The GG genotype was associated with increased odds of epilepsy compared with GC (OR 2.73; 95% CI 1.12–6.65; p = 0.027); the CC genotype showed a non-significant protective trend (OR 0.65; 95% CI 0.17–2.45; p = 0.53). At the allelic level, the C allele was associated with reduced odds of epilepsy (OR 0.54; 95% CI 0.31–0.94; p = 0.030). Multivariable logistic regression adjusted for age and sex yielded effect estimates consistent with the unadjusted analyses. Control genotypes showed modest deviation from Hardy-Weinberg equilibrium (p = 0.022).

Conclusions  The APP rs463946 polymorphism may be associated with epilepsy susceptibility in this Georgian population, with the GG genotype conferring increased risk and the C allele conferring reduced risk. These findings should be interpreted cautiously as hypothesis-generating, pending replication in larger, multicentre studies with comprehensive genetic and phenotypic characterisation.

Keywords  epilepsy; amyloid precursor protein; APP gene; rs463946; single nucleotide polymorphism; genetic predisposition; case-control study; Georgia; Caucasus genetics

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Cover of the Georgian Medical Journal (GMJ), Volume 1, Issue 2 (2026), titled “Health Systems Performance and Quality of Care: Measurement, Improvement, and Outcomes,” with a blue world map background representing global health connectivity. Includes the themes “Quality, Safety, Results” and the publisher Public Health Institute of Georgia.

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05/11/2026

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Vashadze, S., Beridze, M., Kvirkvelia, N., Gorgiladze, K., & Kekenadze, M. (2026). Association of the APP rs463946 Polymorphism with Epilepsy Risk: A Case-Control Study from Georgia. Georgian Medical Journal, 1(2), 1–10. https://doi.org/10.66636/gmj.v1.i2.a110

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Vol. 1 No. 2 (2026): Health Systems Performance and Quality of Care

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Original Research

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Copyright (c) 2026 Shorena Vashadze, Maia Beridze, Nana Kvirkvelia, Keso Gorgiladze, Mariam Kekenadze

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