A systematic review and meta-analysis of the association of ABCC2/ABCG2 polymorphisms with antiepileptic drug responses in epileptic patients

Abstract

PurposeAccumulating evidence indicates that genetic polymorphisms in ATP-binding cassette superfamily members, such asABCC2 and ABCG2, alter responses to antiepileptic drugs (AEDs); however, this evidence is controversial and inconclusive. To provide strong evidence of the association between common polymorphisms in ABCC2 and ABCG2 and AED responses in patients with epilepsy, we performed a systematic review and meta-analysis. MethodsA literature search of electronic databases (PubMed, EBSCO, Ovid and the China National Knowledge Infrastructure) was performed. To evaluate the association of genetic polymorphisms inABCC2 and ABCG2 and risk of AED treatment, we calculated pooled odds ratios (ORs) and 95 % confidence intervals (CIs) using a fixed- or random-effect model. ResultsA significant association of theABCC2 rs717620 polymorphism with resistance to AEDs was found in the overall pooled populations (homozygous comparison: OR = 1.77, 95 % CI, 1.27–2.48; dominant model: OR = 1.23, 95 % CI, 1.06–1.43; recessive model: OR = 1.75, 95 % CI, 1.28–2.40) and Asians (dominant model: OR = 1.21, 95 % CI, 1.03–1.42; recessive model: OR = 1.80, 95 % CI, 1.30–2.50). Using a recessive model, a similarly significant association of ABCC2 rs3740066 with AED resistance was observed in the overall pooled populations (OR = 2.29, 95 % CI, 1.44–3.64) and Asians (OR = 2.53, 95 % CI, 1.56–4.08). However, ABCC2 rs2273697, ABCG2 rs2231137 and rs2231142 were not found to be associated with AED responsiveness. ConclusionThis meta-analysis suggests thatABCC2 rs717620 and rs3740066 are risk factors that predict responses to AEDs in epileptic patients.