The possible effect of SCN1A and SCN2A genetic variants on carbamazepine response among Khyber Pakhtunkhwa epileptic patients, Pakistan.

PURPOSE

and > gene encodes α subunit of the neuronal voltage-gated sodium channel, which is a target for carbamazepine (CBZ). Recent studies have demonstrated that polymorphism of > and > 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 > and > polymorphisms of the and genes affect responsiveness to CBZ.

METHODS

and > 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. and 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 (=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 (=0.003 and =0.01) to have variants ( and ) of gene. Similarly, poor responsders were more likely (=0.0007 and =0.001) to have variant genotypes (, ) of gene at the 3rd month of the therapy.

CONCLUSION

This study demonstrated a significant association between the and and and genotype with CBZ-nonresponsive epilepsy.