Dabla PK, Singh S, Viswas A, Gupta S, Yadav M, Sonkar SC, Koner BC, Serdarevic N. Polymorphic variants in GABA-A receptor and their association with epilepsy and drug resistance: A North Indian cohort study. World J Psychiatry 2025; 15(11): 108964 [DOI: 10.5498/wjp.v15.i11.108964]
Corresponding Author of This Article
Pradeep Kumar 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@gmail.com
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Neurosciences
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Observational Study
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Nov 19, 2025 (publication date) through Nov 3, 2025
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World Journal of Psychiatry
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Dabla PK, Singh S, Viswas A, Gupta S, Yadav M, Sonkar SC, Koner BC, Serdarevic N. Polymorphic variants in GABA-A receptor and their association with epilepsy and drug resistance: A North Indian cohort study. World J Psychiatry 2025; 15(11): 108964 [DOI: 10.5498/wjp.v15.i11.108964]
World J Psychiatry. Nov 19, 2025; 15(11): 108964 Published online Nov 19, 2025. doi: 10.5498/wjp.v15.i11.108964
Polymorphic variants in GABA-A receptor and their association with epilepsy and drug resistance: A North Indian cohort study
Pradeep Kumar Dabla, Swati Singh, Aroop Viswas, Swapan Gupta, Manisha Yadav, Subash C Sonkar, Bidhan C Koner, Nafija Serdarevic
Pradeep Kumar Dabla, Swati Singh, 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 and Research, New Delhi 110002, Delhi, India
Manisha Yadav, Subash C Sonkar, Bidhan C Koner, Multi-disciplinary Research Unit, Maulana Azad Medical College, New Delhi 110002, Delhi, India
Bidhan C Koner, Department of Biochemistry, Maulana Azad Medical College, New Delhi 110002, Delhi, India
Nafija Serdarevic, Institute for Clinical Chemistry and Biochemistry, University of Sarajevo Clinics Center, Sarajevo 71000, Bosnia and Herzegovina
Author contributions: Dabla PK designed and supervised the study, provided facilities for biochemical testing, contributed in data interpretation and preparation and revision of the manuscript; Singh S performed data analysis and drafted the manuscript; Viswas A conducted the experiments and contributed in data collection; Gupta S provided the facility for the enrolment of patients; Yadav M and Sonkar SC helped in performing genetic analysis; Konar BC provided facility for molecular testing; Serdarevic N helped in critical review and data analysis; and all authors have reviewed the entire content of this manuscript and approved for the submission.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Maulana Azad Medical College and Associated Hospitals, approval F1/IEC/MAMC/82/10/2020/No. 225.
Informed consent statement: Informed consent was obtained from all individual participants included in the study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Data is available from the corresponding author on request.
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, 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@gmail.com
Received: April 27, 2025 Revised: May 25, 2025 Accepted: September 1, 2025 Published online: November 19, 2025 Processing time: 191 Days and 0.1 Hours
Abstract
BACKGROUND
Gamma-aminobutyric acid type A receptor has long been acknowledged as a key target in the pathophysiology of epilepsy. The GABRA1 and GABRG2 genes encode the α1 and γ2 subunits of the gamma-aminobutyric acid type A receptor, a key protein implicated in the development of epilepsy. However, the specific association of the GABRA1 IVS11+15 A>G rs2279020 and GABRG2 G3145A rs211013 polymorphisms with antiepileptic drug resistance has been elucidated in only a limited number of investigations.
AIM
To elucidate the association between GABRA1 IVS11+15 A>G rs2279020 and GABRG2 G3145A rs211013 gene mutations and drug resistance in epilepsy patients.
METHODS
A total of 100 epilepsy patients (50 drug responsive and 50 drug resistant subjects) were recruited and rs2279020 - and rs211013 - polymorphism analyzed by restriction fragment length polymorphism - polymerase chain reaction technique.
RESULTS
For GABRA1 rs2279020 polymorphism, AG genotype exhibited risk association with an odds ratio of 0.966 (95% confidence interval = 0.346-2.698) with P value = 0.948; however, this association did not achieve statistical significance (P = 0.948). Additionally, a higher risk association was identified with the GG genotype, with an odds ratio of 1.808 (P = 0.382). GABRG2 rs211013 polymorphism revealed no significant association with drug resistance.
CONCLUSION
The GABRA1 rs2279020 genetic variation is associated with an increased risk for the AG and GG variants, although this association was not statistically significant. Limited investigations have explored the relevance of genetic variations in epilepsy and drug resistance. Longitudinal research is needed to better understand their significance in epilepsy management and to optimize therapeutic strategies.
Core Tip: The limited available data have shown association of gamma-aminobutyric acid (GABA) receptors as a key target in the pathophysiology of epilepsy. Prior studies have hypothesized that polymorphism in genes that encode the α1 and γ2 subunits of the GABA-A receptor protein, alters the channel’s structure-function, potentially leading to medication resistance. However, limited data is available on the relationship between GABA receptor variants and drug resistance in human subjects. In our present study, we aim to elucidate the role of GABA-A subunit variants in the development of anti-epileptic drug resistance, which could inform more personalized treatment strategies for individuals with epilepsy, ultimately improving their health outcomes.
