CACNA2D2 rs56287038:G>T and SCN1A rs2298771:C>T Variants Are Associated with Antiseizure Medication Response in Turkish Epilepsy Patients : A Pilot Study.
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Abstract
Introduction: Epilepsy is a chronic neurological disorder characterized by recurrent seizures, with variants in ion channel genes such as SCN1A, SCN1B, and CACNA2D2 implicated in neuronal excitability. This research aims to explore genetic polymorphisms in the SCN1A, SCN1B, and CACNA2D2 genes among Turkish epilepsy patients and assess their impact on responsiveness to antiseizure medications (ASMs).
Methods: Targeted next-generation sequencing (tNGS) was applied to genomic DNA from 29 patients.
Results: Common 15 variants were analyzed in CACNA2D2 (rs2239801, rs56287038), SCN1A (rs2298771, rs3032638, rs11394960, rs67636132, rs566839, rs1461193, rs6432861, rs2020318) and SCN1B (rs72556351, rs2278995, rs557140301, rs67701503, rs55742440). A statistically significant difference in ASM response was observed in the recessive model of SCN1A rs2298771: C>T (TT vs. CC+CT) (p=0.044), with the TT genotype associated with improved response. CACNA2D2 rs56287038:G>T showed significance in the allelic model (p=0.012); the T allele was found only in resistant patients. SCN1A haplotype analysis revealed reduced C allele frequency in responders (p=0.041). The CT (rs2298771+rs2020318), CG (rs2298771+rs1461193), and CC (rs2298771+rs6432861) haplotypes also showed considerable differences among groups (p=0.041, p=0.023, p=0.041, respectively). Moreover, CTG (rs2298771+rs2020318+rs1461193), CCG (rs2298771+rs6432861+rs1461193), and CTCG (rs2298771+rs2020318+rs6432861+rs1461193) haplotypes were significantly associated with treatment response (p=0.023, p=0.023, p=0.022). However, none of these associations remained statistically significant after false discovery rate (FDR) correction, and all findings should therefore be interpreted as exploratory.
Conclusion: CACNA2D2 rs56287038:G>T and SCN1A rs2298771:C>T may effect ASM response.
期刊介绍：
The biological approach to mental disorders continues to yield innovative findings of clinical importance, particularly if methodologies are combined. This journal collects high quality empirical studies from various experimental and clinical approaches in the fields of Biological Psychiatry, Biological Psychology and Neuropsychology. It features original, clinical and basic research in the fields of neurophysiology and functional imaging, neuropharmacology and neurochemistry, neuroendocrinology and neuroimmunology, genetics and their relationships with normal psychology and psychopathology. In addition, the reader will find studies on animal models of mental disorders and therapeutic interventions, and pharmacoelectroencephalographic studies. Regular reviews report new methodologic approaches, and selected case reports provide hints for future research. ''Neuropsychobiology'' is a complete record of strategies and methodologies employed to study the biological basis of mental functions including their interactions with psychological and social factors.
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