The likelihood approach for potential role of "GABRG2 (C588T, C315T) gene polymorphisms" on the poor response to carbamazepine therapy in Pakhtun population of Pakistan

Background: Gamma-aminobutyric acid A receptor, gamma 2 gene (GABRG2) encode the GABAA receptor which is responsible for fast neuronal inhibition. Polymorphisms in GABGR2 gene affect the clinical response of anti-epileptic drugs (AEDs). Therefore, we carried out an updated study to find the association GABRG2 gene polymorphisms with carbamazepine (CBZ) non-responsive therapy in the Pakhtun population. Methods: A clinical prospective cohort study was conducted in 79 CBZ treated patients upon consent after the approval of Khyber Medical University Advanced Study and Research Board. Blood sample were taken at optimal dose of CBZ at base line, third and sixth months of the treatment. Blood level of CBZ was measure through reverse phase high performance liquid chromatography (HPLC). Restriction fragment length polymorphisms techniques were used to genotype GABRG2 gene in these patients. CBZ responses were evaluated on three and six months of study by measuring the decrease in frequency of seizure per week. Results: The average maximum dose of CBZ was 455 +/- 133 mg/day at baseline, 479 +/- 142 mg/day at third month and 495 +/- 133 mg/day at sixth month of the treatment. CBZ level was found within therapeutic range (4-12 mg/L) without any significant (P > .5) variations among the CC, CT and TT genotypes of GABRG2 (C588T and C315T) gene. But the poor clinical response during CBZ treatment was linked (P < .05) with CT and TT genotypes of GABRG2 (C588T and C315T) gene in Pakhtun Population. Conclusion: A poor response to CBZ was found in variant genotypes (CT and TT) of GABRG2 (C588T and C315T) gene in Pakhtun Population.