Viswas A, Dabla PK, Shrivastav D, Gupta S, Yadav M, Yadav S, Koner BC. SCN1A rs6732655A/T polymorphism: Diagnostic and therapeutic insights for drug-resistant epilepsy. World J Exp Med 2024; 14(3): 94999 [DOI: 10.5493/wjem.v14.i3.94999]
Corresponding Author of This Article
Pradeep K Dabla, 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
Biochemistry & Molecular Biology
Article-Type of This Article
Retrospective 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/
Aroop Viswas, Pradeep K Dabla, Dharmsheel Shrivastav, 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 and Research, New Delhi 110002, Delhi, India
Manisha Yadav, Subhash Yadav, Bidhan Chandra Koner, Multi-disciplinary Research Unit, Maulana Azad Medical College, New Delhi 110002, Delhi, India
Subhash Yadav, Department of Biotechnology, Amity University Gwalior, Gwalior 474005, Madhya Pradesh, India
Bidhan Chandra Koner, Department of Biochemistry, Maulana Azad Medical College, New Delhi 110002, Delhi, India
Author contributions: Viswas A and Yadav S conducted experiments; Dabla PK designed the study and provided facilities for biochemical testing; Dabla PK, Shrivastav D, Viswas A, Yadav M analysed the manuscript; Koner BC provided facilities for molecular testing; Gupta S provided the facility for the enrolment of patients; All authors reviewed and approved the manuscript.
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 or comparable ethical standards. The study involving human participants was approved by the Institutional Ethical Committee of Maulana Azad Medical College and associated hospitals, Delhi, India (F1/IEC/MAMC/82/10/2020/no.225; Dt-14.01.2021).
Informed consent statement: Informed consent was obtained from all individual participants included in the study. Personal interviews were conducted to gather information on ethnicity, seizure frequency, duration of seizures, and compliance.
Conflict-of-interest statement: All authors declared no conflicts of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available upon reasonable request from the corresponding author at pradeep_dabla@yahoo.com.
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 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Pradeep K Dabla, 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: March 29, 2024 Revised: May 20, 2024 Accepted: June 21, 2024 Published online: September 20, 2024 Processing time: 152 Days and 13.9 Hours
Abstract
BACKGROUND
A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs, resulting in heightened mortality rates, psychosocial challenges, and a diminished quality of life. Genetic factors, particularly within the SCN1A gene, and the pro-inflammatory cytokine response is important in intricating the drug resistance in idiopathic epilepsy cases. In this extended study, we determined the correlation of rs6732655A/T single nucleotide polymorphism to understand the causative association of SCN1A gene with epilepsy drug resistance and inflammatory response.
AIM
To find the correlation of SCN1A gene rs6732655A/T polymorphism with the drug-resistant epilepsy and inflammatory response.
METHODS
The study enrolled 100 age and sex-matched patients of both drug-resistant and drug-responsive epilepsy cases. We analysed the rs6732655A/T polymorphism to study its association and causative role in drug-resistant epilepsy cases using restriction fragment length polymorphism technique. The diagnostic performance of interleukin (IL)-1β, IL-6, and high mobility group box 1 (HMGB1) protein levels was evaluated in conjunction with genotypic outcome receiver operating characteristic analysis.
RESULTS
AT and AA genotypes of rs6732655 SCN1A gene polymorphism were associated with higher risk of drug resistance epilepsy. Serum biomarkers IL-6, IL1β and HMGB1 demonstrated diagnostic potential, with cutoff values of 4.63 pg/mL, 59.52 pg/mL and 7.99 ng/mL, respectively, offering valuable tools for epilepsy management. Moreover, specific genotypes (AA and AT) were found to be linked to the elevated levels of IL-1β and IL-6 and potentially reflecting increased oxidative stress and neuro-inflammation in drug-resistant cases supporting the previous reported outcome of high inflammatory markers response in drug resistance epilepsy.
CONCLUSION
SCN1A genotypes AA and AT are linked to higher drug-resistant epilepsy risk. These findings underscore the potential influence of inflammation and genetics on epilepsy treatment resistance.
Core Tip: Genetic factors, including SCN1A gene variants, and their pro-inflammatory cytokine response [interleukin (IL)-1β, IL-6, and high mobility group box 1 protein (HMGB1)], play crucial roles in drug-resistant epilepsy. This study investigates the correlation between SCN1A gene variants (rs6732655A/T) and drug resistance in epilepsy, confirming higher levels of IL-1β, IL-6, and HMGB1 in drug-resistant cases and suggesting specific genotypes (AA and AT) as potential biomarkers for oxidative stress and neuro-inflammation in drug-resistant idiopathic epilepsy.
