Balkan Journal of Medical Genetics

INFLUENCE OF THE SCN1A IVS5N + 5 G>A POLYMORPHISM ON THERAPY WITH CARBAMAZEPINE FOR EPILEPSY
Sterjev Z1,*, Kiteva G2, Cvetkovska E2, Petrov I2, Kuzmanovski I2, Ribarska TJ3, Nestorovska KA1, Matevska N1,Trajkovik-Jolevska S3, Dimovski AJ1, Suturkova, Lj1
*Corresponding Author: Zoran Sterjev, M. Sei. Pharm Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University “St. Cyril and Methodius,” str. Vodnjanska 17, 1000 Skopje, Republic of Macedonia; Tel./Fax:+38-923-120-229; E-mail: zost@ff.ukim.edu.mk
page: 19

DISCUSSION

Our results showed that the frequency of this polymorphism in our patients is similar to that in other population studies [10]. The lack of an association between this polymorphism and the responsiveness to CBZ therapy in our patients did not confi rm the fi ndings of recent reports [5,11] but confi rmed those of one other study [12] (Table 1). These discrepancies may be explained by factors, including sample size, differences in ethnic background of populations, differences in dosing strategies or etiologies of the epilepsy of the studied patients. Patients with the AA genotype needed a higher maintenance dose of CBZ (608  273 mg/day) than patients with the AG and GG genotypes (542  241 and 468  241 mg/ day, respectively). These fi ndings showed interdependence, but did not reach statistical signifi cance, probably because of the insuffi cient number of patients included in the study. The average dose of CBZ needed for a seizure-free period, total plasma concentration of CBZ and dose index were highest in homozygotes for the A allele, indicating that the A allele is a recessive trait that determines the effi cacy of CBZ therapy. These results are similar to those of several large studies [8]. Several in vitro or in vivo studies have demonstrated that the A allele abolished production of the neonatal version of SCN1A channels [9] and that the adult SCN1A channels present in AA homozygotes, have signifi cantly lower sensitivity to CBZ [5,6], which would explain the requirements for higher maintenance doses in our patients. Our results have revealed a difference in the likelihood of response to CBZ, especially at a lower dose, between patients with different genotypes but these differences are diffi cult to translate into clear clinical recommendations. Moreover, the overlap in responses of patients with different genotypes, indicate that other factors also infl uenced CBZ response in our patients. Several other genetic variants in this gene and in other genes related to CBZ metabolism or transport have been described, which may provide further information as to a potential clinical benefi t of pharmacogenetic testing as a tool for individualized therapy in patients with epilepsy [1,13]. Larger clinical studies having the statistical power to evaluate the impact of all these variables are warranted to clarify this issue.

Number 25 VOL. 25 (1), 2022	Number 24 VOL. 24(2), 2021
Number 24 VOL. 24(1), 2021	Number 23 VOL. 23(2), 2020
Number 22 VOL. 22(2), 2019	Number 22 VOL. 22(1), 2019
Number 22 VOL. 22, 2019 Supplement	Number 21 VOL. 21(2), 2018
Number 21 VOL. 21 (1), 2018	Number 21 VOL. 21, 2018 Supplement
Number 20 VOL. 20 (2), 2017	Number 20 VOL. 20 (1), 2017
Number 19 VOL. 19 (2), 2016	Number 19 VOL. 19 (1), 2016
Number 18 VOL. 18 (2), 2015	Number 18 VOL. 18 (1), 2015
Number 17 VOL. 17 (2), 2014	Number 17 VOL. 17 (1), 2014
Number 16 VOL. 16 (2), 2013	Number 16 VOL. 16 (1), 2013
Number 15 VOL. 15 (2), 2012	Number 15 VOL. 15, 2012 Supplement
Number 15 Vol. 15 (1), 2012	Number 14 14 - Vol. 14 (2), 2011
Number 14 The 9th Balkan Congress of Medical Genetics	Number 14 14 - Vol. 14 (1), 2011
Number 13 Vol. 13 (2), 2010	Number 13 Vol.13 (1), 2010
Number 12 Vol.12 (2), 2009	Number 12 Vol.12 (1), 2009
Number 11 Vol.11 (2),2008	Number 11 Vol.11 (1),2008
Number 10 Vol.10 (2), 2007	Number 10 10 (1),2007
Number 9 1&2, 2006	Number 9 3&4, 2006
Number 8 1&2, 2005	Number 8 3&4, 2004
Number 7 1&2, 2004	Number 6 3&4, 2003
Number 6 1&2, 2003	Number 5 3&4, 2002
Number 5 1&2, 2002	Number 4 Vol.3 (4), 2000
Number 4 Vol.2 (4), 1999	Number 4 Vol.1 (4), 1998
Number 4 3&4, 2001	Number 4 1&2, 2001
Number 3 Vol.3 (3), 2000	Number 3 Vol.2 (3), 1999
Number 3 Vol.1 (3), 1998	Number 2 Vol.3(2), 2000
Number 2 Vol.1 (2), 1998	Number 2 Vol.2 (2), 1999
Number 1 Vol.3 (1), 2000	Number 1 Vol.2 (1), 1999
Number 1 Vol.1 (1), 1998

About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact