The ABCB1-C3435T polymorphism likely acts as a risk factor for resistance to antiepileptic drugs

• 8716 epilepsy patients from 38 independent studies were included.
• Six models were used for comparisons of genotypes in meta-analyses.
• Significant associations of C3435T with resistance to AEDs were showed.
• Subgroup analyses based on different factors were done.
• Cumulative meta-analyses by publication year and sample size were adopted.

SummaryPrevious studies have attempted to confirm the association between the ABCB1-C3435T polymorphism and drug-resistant epilepsy and produced discordant findings. A meta-analysis was conducted to assess the role of the C3435T polymorphism in drug-resistance in epilepsy. Databases were obtained from PubMed, Embase, the Chinese Wanfang, CNKI, and Chongqing VIP database, and all relevant studies were compiled up to February 2013. Odds ratios (ORs) were calculated using models of both fixed- and random-effects for comparisons of alleles and genotypes. Subgroup meta-analyses were carried out based on epilepsy subtype, age, therapeutic regimen, definition of drug-responsiveness and drug-resistance using alleles and genotypes models. Publication bias was tested by Begg's test and inverted funnel plot, and heterogeneity was checked by Cochran's Q statistic and the inconsistency index (I2). Cumulative meta-analyses were adopted to test the robustness of the findings. A total of 38 association studies including a total of 8716 subjects, 4037 drug-resistant patients and 4679 drug-responsive epilepsy patients were pooled in this meta-analysis. The association of ABCB1-C3435T with risk of drug-resistance was significant in the overall population (T allele vs. C allele, OR: 1.21; 95%CI: 1.06–1.39; P = 0.006) and in Caucasians, adults, groups treated with various drugs, a ‘>10 seizures in a year’ group based on resistance and a ‘≥2 years seizure free’ group based on response subgroup analysis. The ABCB1-C3435T polymorphism is likely to act as a risk factor for resistance to antiepileptic drugs that needs to be confirmed through further studies.