Dabla PK, Gupta S, Singh S, Viswas A, Yadav M, Sonkar SC, Koner BC. Sodium channel mutation SCN1A T875M, D188V and associated dysfunction with drug resistant epilepsy. World J Psychiatry 2025; 15(2): 100738 [DOI: 10.5498/wjp.v15.i2.100738]
Corresponding Author of This Article
Pradeep Kumar Dabla, MBBS, MD, Professor, Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, 1, Jawaharlal Nehru Marg, 64 Khamba, Raj Ghat, New Delhi 110002, Delhi, India. pradeep_dabla@yahoo.com
Research Domain of This Article
Clinical Neurology
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Pradeep Kumar Dabla, Aroop Viswas, Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi 110002, Delhi, India
Swapan Gupta, Department of Neurology, Govind Ballabh Pant Institute of Postgraduate Medical Education & Research, New Delhi 110002, Delhi, India
Swati Singh, Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Medical Education & Research, New Delhi 110002, Delhi, India
Manisha Yadav, Subash Chandra Sonkar, Bidhan Chandra Koner, Multi-disciplinary Research Unit, Maulana Azad Medical College, New Delhi 110002, Delhi, India
Bidhan Chandra Koner, Department of Biochemistry, Maulana Azad Medical College, New Delhi 110002, Delhi, India
Author contributions: Dabla PK designed and supervised the study, provided facilities for testing, contributed to data interpretation and preparation, revision and finalization of the manuscript; Gupta S provided the facility for the enrolment of patients; Viswas A conducted experiments and contributed to data collection; Singh S performed data analysis and drafted the manuscript; Konar BC, Sonkar SC and Yadav M provided facilities for the genetic analysis; all authors have reviewed the entire content of this manuscript and approved it for submission.
Institutional review board statement: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments. The study was approved by the Institutional Ethical Committee of Maulana Azad Medical College and associated hospitals, New Delhi, India (F1/IEC/MAMC/82/10/2020/no.225).
Informed consent statement: Informed consent was obtained from all participants included in the study. Personal interviews were conducted to gather information on ethnicity, seizure frequency, duration of seizures, and medication compliance.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: Technical appendix, statistical code and dataset are available from the corresponding author, Dr Pradeep Kumar Dabla.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Pradeep Kumar Dabla, MBBS, MD, Professor, Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, 1, Jawaharlal Nehru Marg, 64 Khamba, Raj Ghat, New Delhi 110002, Delhi, India. pradeep_dabla@yahoo.com
Received: August 24, 2024 Revised: November 30, 2024 Accepted: December 20, 2024 Published online: February 19, 2025 Processing time: 142 Days and 16.6 Hours
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. χ2 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.
Core Tip: Epilepsy is the most common paroxysmal neurological disorder and a significant global health burden. A subset of patients are resistant to anti-epileptic drugs, leading to increased mortality and decreased quality of life. Mutations in genes encoding neuronal voltage-gated sodium channels have been linked to inherited forms of epilepsy. This study investigates the correlation between SCN1A gene variants rs121918623 and SCN1A rs121917953 and drug resistance in epilepsy suggesting specific genotypes as potential biomarkers in drug-resistant idiopathic epilepsy.
