ABCC2 rs2273697, rs717620, rs3740066 Polymorphisms and Antiseizure Medication Resistance: A Systematic Review and Meta-Analysis

Objective Genetic variations in the ABCC2 gene have been proposed to influence resistance to antiseizure medications, but published findings to date are inconsistent. We aimed to systematically assess the association of three ABCC2 polymorphisms, rs2273697 (c.1249G > A, p.Val417Ile), rs717620 (c.-24C > T, 5′UTR), and rs3740066 (c.3972C > T, p.Lys1324Lys), with drug-resistant epilepsy and analyzed the statistical power, effect sizes, and required sample sizes. Methods Searches covered the National Center for Biotechnology Information dbSNP “publications” pages, Cochrane, Scopus, and Springer Nature Link databases (2003–2025). Effect size (Cohen’s w) and power were estimated using G*Power 3.1, and random-effects meta-analyses were performed using sensitivity and publication-bias assessments. Results Nineteen studies (2,429 drug-resistant and 2,446 drug-responsive patients) met the inclusion criteria. The meta-analysis showed that rs717620 was significantly associated with drug-resistant epilepsy: allelic model (T vs. C) OR 1.25, 95% CI 1.06–1.48; recessive model OR 1.63, 95% CI 1.13–2.37; and homozygous comparison (TT vs. CC) OR 1.79, 95% CI 1.17–2.74 with low-to-moderate heterogeneity and no evidence of small-study bias. The pooled estimates for rs2273697 and rs3740066 were null across the genetic models. High and very high statistical power for rs2273697 and rs3740066 were achieved in 50.0% and 37.5%, whereas rs717620 achieved 38.4% of the high-power studies. Median increases of 348%, 322%, and 289% are required to achieve a study power of 0.8. Conclusion The rs717620 (c.-24C > T, 5′ UTR variant) TT genotype showed the greatest susceptibility to antiseizure medication resistance. Large multicenter diverse studies with standardized outcomes and haplotype analyses are needed to validate rs717620 as a clinical risk marker.