Association of ABCB1 gene polymorphism (C1236T and C3435T) with refractory epilepsy in Iraqi patients

The mechanisms of refractory epilepsy (RE) are most likely multifactorial, involving environmental, genetic, as well as disease- and drug-related factors. We aimed to study is to investigate the possible association of two ABCB1 gene polymorphism (C3435T and C1236T) with the development of RE in Iraqi patients. One hundred patients with either generalized tonic–clonic seizures, myoclonic epilepsy, or absence epilepsy comprised of 60 patients responsive to AEDs and 40 patients who were refractory to treatment who used multi AEDs for at least one month were studied. Fifty family-unrelated age- and sex-matched healthy subjects represent the control group. ABCB1 gene fragments corresponding to two targeted polymorphisms were amplified with conventional polymerase chain reaction using specific sets of primers. Genotyping was performed by restriction fragment length polymorphism (RFLP) technique. Epileptic patients refractory to AEDs showed a significantly higher frequency of CC genotypes of C3435T polymorphism than controls. Allele C was significantly higher in patients than controls and far more frequent among patients with RE. C1235T polymorphism had no significant role neither in the incidence of epilepsy nor in the AEDs resistance. The CT haplotype was more frequent among patients refractory to AEDs. In contrast, the haplotype block TT was more frequent among responsive (41.3%) than refractory patients (28.7%) (p = 0.068). The CC genotype and C allele of the C3435T polymorphism can increase the risk of RE. The haplotype block CT of C3435T and C1236T can predispose for epilepsy as well as the drug resistance.