Abstract
BackgroundEthnicity variation is one of the main factors that may affect drug response in clinical practice. As MTHFR gene affects different transcriptome and proteome which affect the clinical response of drugs. Purpose of the current study was to observe possible variations in plasma levels of carbamazepine monotherapy and seizures’ control in Pakhtun population of Khyber Pakhtunkhwa (KP) in the context of MTHFR (C677T and A1298C) gene polymorphisms.MethodsBlood was collected from the epileptic patients treated with carbamazepine monotherapy for the first time following respective oral doses on its steady state concentration after 3 h of morning dose at 3rd and 6th month of the therapy. Plasma carbamazepine levels were determined using reverse phase high performance liquid chromatography after method validation. MTHFR (C677T, AA298C) gene was genotyped. Patients were followed on 3rd and 6th month of the therapy for monitoring of response to carbamazepine therapy.ResultsFollowing for 3rd and 6th month of duration of carbamazepine therapy, poor seizure controlled patients were more likely noticed in heterozygous variants (677CT and 1298 AC) of MTHFR gene (P < 0.05). There was no significant (P > 0.05) difference in the dose and plasma level of carbamazepine among different genotypes of MTHFR (C677T and A1298C) gene. Similarly, the difference in dose and plasma level of carbamazepine was not significant (P > 0.05) in the responder and non-responder people with epilepsy.ConclusionOur study suggests that heterozygous variants of MTHFR (C677T and A1298C) gene are associated with poor seizure control in Pakhtun population of KP despite the fact that plasma level of carbamazepine were found within the therapeutic range.
Highlights
Ethnicity variation is one of the main factors that may affect drug response in clinical practice
We have recently observed that heterozygous variant (677CT and 1298 AC) of Methylene tetra hydrofolate reductase (MTHFR) gene frequently experienced low level of vitamin B6, which helps in synthesis of GABA, inhibitory neurotransmitters in carbamazepine treated patients
The current work is carried to correlate the clinical prognosis in heterozygous variant of MTHFR gene and GABRG2 gene, which are deficient in vitamin B6 as per our recently published work [14]
Summary
Ethnicity variation is one of the main factors that may affect drug response in clinical practice. Purpose of the current study was to observe possible variations in plasma levels of carbamazepine monotherapy and seizures’ control in Pakhtun population of Khyber Pakhtunkhwa (KP) in the context of MTHFR (C677T and A1298C) gene polymorphisms. We have recently observed that heterozygous variant (677CT and 1298 AC) of MTHFR gene frequently experienced low level of vitamin B6, which helps in synthesis of GABA, inhibitory neurotransmitters in carbamazepine treated patients. The current study is focused on the possible pharmacogenomics effect of MTHFR (C677T and A1298C) gene polymorphisms on carbamazepine monotherapy and its subsequent control on seizures with carbamazepine therapy in Pakhtun population of Khyber Pakhtunkhwa
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