Sodium channel mutation SCN1A T875M,D188V and associated dysfunction with drug resistant epilepsy  

作　　者：Pradeep Kumar Dabla Swapan Gupta Swati Singh Aroop Viswas Manisha Yadav Subash Chandra Sonkar Bidhan Chandra Koner 

机构地区：[1]Department of Biochemistry,Govind Ballabh Pant Institute of Postgraduate Medical Education and Research,New Delhi 110002,Delhi,India [2]Department of Neurology,Govind Ballabh Pant Institute of Postgraduate Medical Education&Research,New Delhi 110002,Delhi,India [3]Department of Biochemistry,Govind Ballabh Pant Institute of Postgraduate Medical Education&Research,New Delhi 110002,Delhi,India [4]Multi-disciplinary Research Unit,Maulana Azad Medical College,New Delhi 110002,Delhi,India [5]Department of Biochemistry,Maulana Azad Medical College,New Delhi 110002,Delhi,India

出　　处：《World Journal of Psychiatry》2025年第2期41-47,共7页世界精神病学杂志(英文)

摘　　要：BACKGROUND The NaV1.1 sodium channel alpha subunit,encoded by SCN1A,is crucial for initiating and propagating action potentials in neurons.SCN1A gene has long been an established target in the etiology and therapy of epilepsy.However,very few studies have investigated the relevance of genetic variations in epilepsy and anti-epileptic drug resistance.AIM To investigate associations between polymorphisms,rs121917953 T/A and rs121918623 C/T,and drug resistance in epilepsy patients in the north Indian population.METHODS A total of 100 age-and sex-matched epilepsy patients(50 drug responsive and 50 drug resistant subjects)were recruited and SCN1A rs121918623 C/T*and rs121917953 T/A*polymorphisms were analyzed by the allele specific-PCR technique.χ^(2)and Fisher’s exact test were used to estimate differences between the distribution of SCN1A rs121918623 and rs121917953 gene polymorphisms among various groups.The association between distinct rs121917953 genotypes and drug resistance was analyzed using logistic regression analysis.RESULTS For the SCN1A rs121917953 T/A*(D188V)polymorphism,a significantly higher proportion of individuals with AT genotype were observed in the drug-resistant group as compared to the drug-responsive group.Additionally,a higher risk association was exhibited by AT genotype for drug resistance with an odds ratio of 3.51 and P value=0.017.For the SCN1A rs121918623 C/T*(T875M)polymorphism,no significant difference in genotype distribution was observed between the drug-resistant and drug-sensitive groups.CONCLUSION Our findings indicate that the SCN1A polymorphism D188V is associated with a higher risk of drug resistance for the AT variant as compared to the homozygous TT wild-type.Further research is needed at the functional level and in larger cohorts to determine the potential of these genes as a therapeutic target in epilepsy subjects.

关 键 词：EPILEPSY Single nucleotide polymorphisms Drug-resistant epilepsy SCN1A receptor SCN1A rs121918623 and SCN1A rs121917953 gene polymorphism 

分 类 号：R742.1[医药卫生—神经病学与精神病学]