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

IF 3.9 4区 医学 Q1 PSYCHIATRY
Pradeep Kumar Dabla, Swapan Gupta, Swati Singh, Aroop Viswas, Manisha Yadav, Subash Chandra Sonkar, Bidhan Chandra Koner
{"title":"Sodium channel mutation <i>SCN1A</i> T875M, D188V and associated dysfunction with drug resistant epilepsy.","authors":"Pradeep Kumar Dabla, Swapan Gupta, Swati Singh, Aroop Viswas, Manisha Yadav, Subash Chandra Sonkar, Bidhan Chandra Koner","doi":"10.5498/wjp.v15.i2.100738","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The NaV1.1 sodium channel alpha subunit, encoded by <i>SCN1A</i>, is crucial for initiating and propagating action potentials in neurons. <i>SCN1A</i> 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.</p><p><strong>Aim: </strong>To investigate associations between polymorphisms, rs121917953 T/A and rs121918623 C/T, and drug resistance in epilepsy patients in the north Indian population.</p><p><strong>Methods: </strong>A total of 100 age- and sex-matched epilepsy patients (50 drug responsive and 50 drug resistant subjects) were recruited and <i>SCN1A</i> rs121918623 C/T* and rs121917953 T/A* polymorphisms were analyzed by the allele specific-PCR technique. <i>χ</i> <sup>2</sup> and Fisher's exact test were used to estimate differences between the distribution of <i>SCN1A</i> rs121918623 and rs121917953 gene polymorphisms among various groups. The association between distinct rs121917953 genotypes and drug resistance was analyzed using logistic regression analysis.</p><p><strong>Results: </strong>For the <i>SCN1A</i> 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 <i>P</i> value = 0.017. For the <i>SCN1A</i> rs121918623 C/T* (T875M) polymorphism, no significant difference in genotype distribution was observed between the drug-resistant and drug-sensitive groups.</p><p><strong>Conclusion: </strong>Our findings indicate that the <i>SCN1A</i> 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.</p>","PeriodicalId":23896,"journal":{"name":"World Journal of Psychiatry","volume":"15 2","pages":"100738"},"PeriodicalIF":3.9000,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758033/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Journal of Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.5498/wjp.v15.i2.100738","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
引用次数: 0

Abstract

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.

钠通道突变SCN1A T875M、D188V及相关功能障碍与耐药癫痫
背景:由SCN1A编码的NaV1.1钠通道α亚基对神经元动作电位的启动和传播至关重要。SCN1A基因长期以来一直是癫痫病因学和治疗的确定靶点。然而,很少有研究调查癫痫遗传变异与抗癫痫药物耐药性的相关性。目的:探讨印度北部人群癫痫患者rs121917953 T/A和rs121918623 C/T多态性与耐药的关系。方法:招募年龄和性别匹配的癫痫患者100例(药物反应组50例,耐药组50例),采用等位基因特异性pcr技术分析SCN1A rs121918623 C/T*和rs121917953 T/A*多态性。采用χ 2和Fisher精确检验估计SCN1A rs121918623和rs121917953基因多态性在不同人群中的分布差异。采用logistic回归分析不同rs121917953基因型与耐药的相关性。结果:SCN1A rs121917953 T/A* (D188V)多态性,耐药组AT基因型个体比例明显高于药物反应组。AT基因型与耐药风险相关性较高,比值比为3.51,P值= 0.017。SCN1A rs121918623 C/T* (T875M)多态性在耐药组和药敏组之间的基因型分布无显著差异。结论:我们的研究结果表明,与纯合子TT野生型相比,SCN1A多态性D188V与AT变体更高的耐药风险相关。需要在功能水平和更大的队列中进行进一步的研究,以确定这些基因作为癫痫患者治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
6.50%
发文量
110
期刊介绍: The World Journal of Psychiatry (WJP) is a high-quality, peer reviewed, open-access journal. The primary task of WJP is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of psychiatry. In order to promote productive academic communication, the peer review process for the WJP is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJP are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in psychiatry.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信