The possible effect of SCN1A and SCN2A genetic variants on carbamazepine response among Khyber Pakhtunkhwa epileptic patients, Pakistan
Received 19 July 2018
Accepted for publication 9 September 2018
Published 21 November 2018 Volume 2018:14 Pages 2305—2313
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Professor Garry Walsh
Haleema Rehana Nazish,1 Niaz Ali,1 Shakir Ullah1,2
1Institute of Basic Medical Science, Khyber Medical University, Peshawar, Khyber Pakhtunkhwa, Pakistan; 2Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong 515041, People’s Republic of China
Purpose: SCN1A (3184 A>G) and SCN2A (56G>A) gene encodes a subunit of the neuronal voltage-gated sodium channel, which is a target for carbamazepine (CBZ). Recent studies have demonstrated that polymorphism of SCN1A (3184 A>G) and SCN2A (56G>A) was associated with use of CBZ. However, it has not been determined whether the polymorphism affects CBZ or other antiepileptic drug responsiveness. The aim of the study was to establish whether the SCN1A (3184 A>G) and SCN2A (56G>A) polymorphisms of the SCN1A and SCN2A genes affect responsiveness to CBZ.
Methods: SCN1A (3184 A>G) and SCN2A (56G>A) gene polymorphisms were genotyped in 93 Khyber Pakhtunkhwa epileptic patients treated with CBZ. The association between CBZ responsiveness and the polymorphism was estimated by adjusting for clinical factors affecting the outcome of therapy. The number of seizure episodes was documented at baseline, and the therapy of each of the 93 patients was followed up. The plasma level of CBZ was determined using reverse-phase high-performance liquid chromatography. SCN1A and SCN2A genes were genotyped using RFLP. Data were analyzed using Graph Pad Prism 6.
Results: Mean age of the patients was 18.6±9.3 at the 3rd month and 18.7±9.5 at the 6th month. The baseline dose of CBZ was 468±19.8 mg/d and titrated at the rate of 48±1.4 and 4.0±0.2 mg/d. The difference in plasma level of CBZ was significant (P=0.004) between 3rd and 6th month among different genotypes of SCN1A gene in nonresponder and responder patients. At the 3rd month of the therapy, the poor responders were more likely (P=0.003 and P=0.01) to have variants (3184AG and 3184GG) of SCN1A gene. Similarly, poor responsders were more likely (P=0.0007 and P=0.001) to have variant genotypes (56GA, 56AA) of SCN2A gene at the 3rd month of the therapy.
Conclusion: This study demonstrated a significant association between the SCN1A (3184 AG and GG) and SCN2A (56GA and AA) genotype with CBZ-nonresponsive epilepsy.
Keywords: carbamazepine, epilepsy, resistance, SCN1A gene and SCN2A gene polymorphisms, clinical response
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