The lack of influence of IVS5-91 G>A polymorphism of the SCN1A gene on efficacy of lamotrigine in patients with focal epilepsy

ABSTRACT

Background: IVS5-91G>A (rs3812718) polymorphism of the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene has been associated with inadequate responsiveness to common antiepileptic drugs which act as sodium channel blockers. This study was performed to investigate the effect of IVS5-91G>A (rs3812718) polymorphism on lamotrigine (LTG) efficacy in a cohort of patients with non-lesional focal epilepsy taking LTG as monotherapy.

Methods: A total of 100 of patients with non-lesional focal epilepsy on LTG monotherapy was included in this prospective interventional study. After reaching a stable dose of LTG patients were followed-up for 12 consecutive months. LTG responsiveness was defined as a 75% or more reduction in seizure frequency on a stable dose of LTG. Genotyping was performed at the end of the study using standard procedures and data were correlated with clinical data.

Results: There were no significant differences in the prevalence of responsiveness to LTG between carriers of different genotypes. Average maintenance LTG doses in the responder group differed by genotype in the order AA>GA>GG, but these differences did not reach statistical significance.

Conclusion: Our data suggest lack of association between SCN1A IVS5-91G>A (rs3812718) polymorphism and response to LTG.

KEYWORDS:

• Epilepsy
• lamotrigine
• SCN1A
• polymorphism

Acknowledgments

We thank Barbara Every, ELS, of BioMedical Editor, for English language editing.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Notes on contributors

Ivana Markovic

Ivana Markovic, MD, PhD is a neurologist working at the Department of Neurology and the Referral centre of Croatian Ministry of Health for preoperative assessment of patients with pharmacoresistant epilepsy at the University hospital Dubrava in Zagreb. She is also a neurology lecturer at the Faculty of Dental Medicine and Health at the J.J. Strossmayer University in Osijek. Her main interest is in management of pharmacoresistance in adult patients with epilepsy.

Natasa Pejanovic-Skobic

Natasa Pejanovic-Skobic, MD, MSc is working as an adult neurologist at the Department of Clinical neurology EEG laboratory, video EEG monitoring unit and epilepsy outpatient clinic at the University Clinical Hospital Mostar in Bosnia and Herzegovina. She finished several regional and international neurological courses including EEG and Epilepsy Course at the Cleveland Clinic Epilepsy Center in 2013.

Nada Bozina

Nada Bozina, MD, PhD is a professor of pharmacology at the University of Zagreb School of Medicine. She works as the head of the Clinical unit for pharmacogenomics and therapy individualization at the University hospital Centre Zagreb. She worked as a researcher at the Imperial College London, Royal Postgraduate Medical School - Hammersmith (UK), the Hatfield Polytechnic, University of Hertfordshire (UK) and at the University of California Davis (USA). Her expertise is the role of pharmacogenetics and pharmacogenomics in the field of therapy individualization.

Ivana Susak Sporis

Ivana Susak Sporis, MD is working as a neurologist at the Department of Neurology at the University hospital Dubrava Zagreb, Croatia. She is a team member at the Referral centre of Croatian Ministry of Health for preoperative assessment of patients with pharmacoresistant epilepsy. Her main interest is in therapeutic and surgical management of epilepsy.

Davor Sporis

Davor Sporis, MD, PhD is working as an associate professor of neurology at the Faculty of Dental Medicine and Health at the University of J.J. Strossmayer in Osijek. He works as the neurologist and the head of Epilepsy unit at the Department of Neurology at the University hospital Dubrava Zagreb, Croatia. He is also epileptologist at the Referral centre of Croatian Ministry of Health for preoperative assessment of patients with pharmacoresistant epilepsy. His main interests are in the preoperative assessment of patients with pharmacoresistant epilepsy.

Silvio Basic

Silvio Basic, MD, PhD is working as an epileptologist and the head of the Department of Neurology at the University Hospital Dubrava in Zagreb, head of the Referral Centre of Croatian Ministry of Health for preoperative assessment of patients with pharmacoresistant epilepsy, professor of neurology at the University of Applied Health Sciences in Zagreb, head of the Department of neurology and neurosurgery and professor of neurology at the Faculty of Dental Medicine and Health at the University of J. J. Strossmayer in Osijek. His main interest are in pathophysiology and surgical management of pharmacoresistant epilepsy.