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Updated: May 13, 2026

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons
Published on: June 6, 2025
SCN1AIVS5-91G>A polymorphism is associated with susceptibility to epilepsy but not with drug responsiveness
Ritu Kumari1, Ram Lakhan, Surendra Kumar
1Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, India.
Abstract:
Sodium channel alpha subunit type 1 (SCN1A) is voltage gated ion channel which plays critical role in membrane excitability. A common SCN1A IVS5-91G>A (rs3812718) allele has been attributed to be a possible modifying factor for epilepsy susceptibility and therapeutic response. In the present study, we enrolled 485 epilepsy patients and 298 age-sex matched controls free of neurological deficits. Therapeutic response of carbamazepine/oxcarbamazepine (CBZ/OXC) and other antiepileptic drugs were observed in terms of drug responsiveness and drug resistance. Genotyping of SCN1A IVS5-91G>A is done by Taqman custom designed assay; in a real time7500HT System. We observe highly significant association [(P-values for GA (P = 6.58 × 10(-5), OR = 2.13, 95% CI = 1.47-3.09) and AA (P = 4.11 × 10(-9), OR = 3.59, 95% CI = 2.35-5.50)] at variant genotypes as well as A allele (P = 6.92 × 10(-11)), OR = 1.99, 95%, CI = 1.62-2.45) in epilepsy patients versus control subjects. The relative risk for epilepsy susceptibility due to variant containing genotypes (GA + AA) was also significant (P = 1.64 × 10(-5); OR = 2.56; 95% CI = 1.80-3.65) when compared with homozygous wild-type GG. The risk in recessive model (P = 1.34 × 10(-5); OR = 2.12; 95% CI = 1.51-2.97) was also apparent when compared with GA + GG. In case-only analysis, we evaluated the effect of SCN1A IVS5-91G>A polymorphism with drug resistance of anti-epileptic drug therapies. However, we did not observe significant associations either with patients showing drug resistance to CBZ/OXC monotherapy or polytherapy. In conclusion, we report that SCN1AIVS5-91G>A polymorphism is associated with epilepsy susceptibility but not with drug responsiveness in epilepsy patients from North India.
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