Epilepsy control with carbamazepine monotherapy from a genetic perspective

Area of Science:

• Pharmacogenomics
• Clinical Pharmacy
• Molecular Biology

Background:

• Drug response varies significantly with ethnicity.
• The Methylenetetrahydrofolate reductase (MTHFR) gene influences drug metabolism and clinical outcomes.
• Understanding genetic variations is crucial for personalized medicine.

Purpose of the Study:

• To investigate the association between MTHFR gene polymorphisms (C677T and A1298C) and carbamazepine response in the Pakhtun population.
• To evaluate plasma carbamazepine levels and seizure control in relation to MTHFR genotypes.
• To explore ethnic variations in drug response within the Khyber Pakhtunkhwa (KP) region.

Main Methods:

• Collected blood samples from epileptic patients on carbamazepine monotherapy at 3 and 6 months.
• Quantified plasma carbamazepine levels using validated High-Performance Liquid Chromatography (HPLC).
• Genotyped MTHFR (C677T and A1298C) gene polymorphisms and monitored seizure control.

Main Results:

• Heterozygous MTHFR variants (677CT and 1298AC) were associated with significantly poorer seizure control (P < 0.05).
• No significant differences in carbamazepine dose or plasma levels were observed across different MTHFR genotypes.
• Responder and non-responder groups showed no significant differences in carbamazepine dose or plasma levels.

Conclusions:

• Heterozygous MTHFR variants are linked to inadequate seizure control in the Pakhtun population.
• Carbamazepine plasma levels remained within the therapeutic range despite poor seizure control in certain genotypes.
• Genetic profiling of MTHFR may aid in predicting carbamazepine treatment efficacy in this ethnic group.