title: The effects of ABCC2 G1249A polymorphism on the risk of resistance to antiepileptic drugs: a meta-analysis of the literature.
abstract: OBJECTIVE
  The G1249A variant of the multidrug resistance-associated protein 2 (ABCC2) gene may be associated with the development of antiepileptic drug (AED) resistance. Although numerous studies have investigated the association between the G1249A variant and the risk of drug resistance in epilepsy, the results of these studies have been inconclusive. To assess the role of G1249A polymorphism in drug resistance in epilepsy, a meta-analysis was performed.
  
  
  METHODS
  We systematically reviewed relevant studies retrieved by the PubMed and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated based on the date extracted from the studies to evaluate the strength of association. We also analyzed the heterogeneity and sensitivity of each report and the publication bias of the studies.
  
  
  RESULTS
  A total of 6 published studies, involving 2213 patients (1100 patients with drug-resistant epilepsy and 1113 controls with drug-responsive epilepsy) were reviewed in the present meta-analysis. The overall results indicated that the variant genotypes were associated with a significantly decreased risk of AED resistance (AA vs. GG: OR=0.372, 95% CI=0.182-0.762; recessive model: OR=0.399, 95% CI=0.200-0.795) (fixed-effects model). A stratified analysis by ethnicity showed similar findings for Caucasians in an additive model (A vs. G: OR=0.700, 95% CI=0.494-0.992).
  
  
  CONCLUSIONS
  The meta-analysis suggests that the ABCC2 G1249A polymorphism is significantly associated with a decreased risk of AED resistance. However, further functional investigations are warranted to validate the association.
authors: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University , Nanjing, China .
authors: Pin
authors: P
authors: Chen
authors: Qing
authors: Q
authors: Yan
authors: Haitao
authors: H
authors: Xu
authors: Ailin
authors: A
authors: Lu
authors: Peng
authors: P
authors: Zhao
mesh_terms: D019943:Amino Acid Substitution; D000927:Anticonvulsants / Q000627:therapeutic use*; D004351:Drug Resistance / Q000235:genetics*; D004827:Epilepsy / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014633:Valine / Q000235:genetics
chemical_list: D000927:Anticonvulsants; D007532:Isoleucine; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014633:Valine; C000715087:ABCC2 protein, human