Background Epilepsy is a chronic disorder with a higher prevalence in low- and middle-income countries. ATP-binding cassette superfamily B1 ( ABCB1 ) lies not only in its potential influence on the resistance to antiepileptic drugs but also in its possible role in the occurrence of epilepsy. Purpose To evaluate the association of ABCB1 polymorphisms, c.1236C > T(rs1128503), c.2677G > T(rs2032582), and c.3435C > T(rs1045642), with epilepsy susceptibility in the Jordanian cohort. Subjects and methods: Eighty-six cases of patients with epilepsy were analyzed using polymerase chain reaction (PCR) for ABCB1 c.1236C > T, c.2677G > T, and c.3435C > T gene variants. The proportions of genotype and allele in the epilepsy group were compared with one hundred healthy controls who were previously also analyzed by PCR. Results The C alleles of the ABCB1 polymorphisms c.1236C > T and c.3435C > T were more prevalent in the epilepsy group than in controls. The patients with epilepsy were less likely to have the TT genotype compared with controls (concerning ABCB1 c.1236C > T) (OR _{TT vs CC} =0.42; 95%CI = [0.19–0.91]; p = 0.019). The CC genotype of ABCB1 c.3435C > T was more frequent in epileptics than healthy people (OR _{CC vs TT} =4.3; 95%CI = [1.8–9.95]; p = 0.0007). No significant difference in ABCB1 c.2677G > T allelic and genotypic frequencies was observed between epileptic cases and healthy volunteers. Conclusion Our results revealed that ABCB1 c.1236C > T and c.3435C > T genotypes and alleles play a role in susceptibility to epilepsy. Also, the present study identified no significant association between ABCB1 c.2677G > T and the occurrence of epilepsy.

Background: We investigated whether common variants in SCN1A are associated with antiepileptic drug (AED) non-response in Jordanian patients with epilepsy. Methods: We recruited 114 patients (105 successfully genotyped) and Sanger-sequenced five loci spanning rs6432860 and its flanking region of rs1531380, rs1531379, rs1531378, and rs10198801. Genotype–response associations were tested using contingency analyses and multivariable logistic regression adjusting for age at the time of the interview, number of AEDs, and carbamazepine use. Pre-specified secondary analyses included (i) stratification by AED class (voltage-gated sodium channel [VGSC]-acting vs. non-VGSC agents) and (ii) sensitivity analyses using alternative non-response thresholds (seizures > 0/year and ≥4/year). Linkage disequilibrium (LD) and exact Hardy–Weinberg equilibrium (HWE) tests were evaluated. Cohort minor allele frequencies (MAFs) were compared with global population estimates. Results: The four upstream previously cataloged intronic variant SNPs (rs1531380, rs1531379, rs1531378, and rs6432860) were in a complete pattern of LD association in this population (D′ = 1; r^{2 =} 1) whereas each upstream variant with rs10198801 showed D′ = 1 with inverse correlation (r ≈ −0.53). All loci conformed to the exact HWE tests. Upstream variants had novel associations with a non-response in unadjusted analyses and remained significant after adjustment (genotype aOR = 2.8; 95% CI = 1.1–7.2; p value = 0.03), alongside independent effects of carbamazepine use (aOR = 3.3; 95% CI = 1.3–8.0; p value = 0.009) and a number of AEDs (aOR = 0.17; 95% CI = 0.06–0.50; p value = 0.002). In AED-class stratification, upstream additional intronic variants had novel associations with a non-response among VGSC-treated patients (OR = 3.8; 95% CI = 1.1–13.6; p value = 0.03) whereas rs10198801 was associated among non-VGSC patients (OR = 7.9; 95% CI = 0.9–70; p value = 0.04). Findings were robust using a ≥4 seizures/year threshold (recessive model significant) but not using any seizures > 0/year. Cohort MAFs for upstream variants (~48.6%) exceeded European, African, and Asian estimates. Significance: SCN1A upstream intronic variation has a novel association with AED non-response in the Jordanian cohort, shows mechanism-aligned patterns by AED class, persists after covariate adjustment and under a clinically used seizure-frequency threshold, and warrants ancestry-informed replication and functional validation.

Background: Epilepsy is a chronic disorder with a higher prevalence in low- and middle-income countries. ATP-binding cassette superfamily B1 (ABCB1) not only has a potential influence on the resistance to antiepileptic drugs but also plays a possible role in the occurrence of epilepsy. Purpose: To evaluate the association of ABCB1 polymorphisms, c.1236C>T (rs1128503), c.2677G>T (rs2032582), and c.3435C>T (rs1045642), with epilepsy susceptibility in a Jordanian cohort. Subjects and methods: Eighty-six cases of patients with epilepsy were analyzed using polymerase chain reaction (PCR) for ABCB1 c.1236C>T, c.2677G>T, and c.3435C>T gene variants. The proportions of genotypes and alleles in the epilepsy group were compared with one hundred healthy controls who were previously also analyzed by PCR. Results: The C alleles of the ABCB1 polymorphisms c.1236C>T and c.3435C>T were more prevalent in the epilepsy group than in controls. The patients with epilepsy were less likely to have the TT genotype compared with controls (concerning ABCB1 c.1236C>T) (OR_{TT vs. CC} = 0.42; 95% CI = [0.19–0.91]; p = 0.019). The CC genotype of ABCB1 c.3435C>T was more frequent in epileptics than healthy people (OR_{CC vs. TT} = 4.3; 95% CI = [1.8–9.95]; p = 0.0007). No significant difference in ABCB1 c.2677G>T allelic and genotypic frequencies was observed between epileptic cases and healthy volunteers. Conclusion: Our findings suggest that ABCB1 c.1236C>T and c.3435C>T variants were associated with epilepsy susceptibility in this Jordanian cohort, whereas no significant association was observed for c.2677G>T. These findings should be interpreted cautiously because of the modest sample size and require validation in larger, independent studies.