The ABCC2 c.-24C>T Polymorphism Increases the Risk of Resistance to Antiepileptic Drugs: A Meta-Analysis

J Clin Neurosci. 2017 Mar;37:6-14. doi: 10.1016/j.jocn.2016.10.014. Epub 2016 Nov 2.

Abstract

Several studies examined a possible link between multidrug resistance-associated protein 2 (ABCC2) gene variants and the risk of resistance to antiepileptic drugs (AEDs) in epilepsy, but the results were contradictory. In this study, a meta-analysis was conducted to assess the relevance of ABCC2 common variants (c.-24C>T, c.1249G>A, c.3972C>T) with the response risk of AEDs. We searched Embase, PubMed, the Cochrane Library and CNKI databases for case-control studies published through May 2016 that evaluated the role of ABCC2 gene variants in pharmacoresistance to AEDs. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated to assess the strength of associations between the ABCC2 c.-24C>T, c.1249G>A and c.3972C>T variants and the risk of resistance to AEDs using an allele frequency model, dominant model and recessive model. Subgroup analyses were performed by ethnicity and the definition of drug-resistance. A total of 13 published studies involving 4300 patients (2261 patients with drug-resistant epilepsy and 2039 controls with drug-responsive epilepsy) met the selection criteria. We observed that the variant c.-24C>T was associated with a significantly increased risk of AED resistance (TT+CT vs CC: OR=1.24, 95%CI=1.06-1.46, p=0.009; TT vs CT+CC: OR=1.90, 95%CI=1.31-2.76, p=0.0008; T vs C: OR=1.27, 95%CI=1.11-1.46, p=0.0006). However, we identified no significant association of the ABCC2 c.1249G>A, c.3972C>T variants and haplotypes with the response to anticonvulsant drug in the overall population. In summary, these observations suggest that the ABCC2 c.-24C>T polymorphism is a likely risk factor for resistance to AEDs.

Keywords: ABCC2; Antiepileptic drugs; Epilepsy; Meta-analysis; Polymorphism.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Anticonvulsants / therapeutic use*
  • Drug Resistance / genetics*
  • Epilepsy / drug therapy*
  • Epilepsy / genetics
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Multidrug Resistance-Associated Proteins / genetics*
  • Polymorphism, Single Nucleotide*

Substances

  • Anticonvulsants
  • Multidrug Resistance-Associated Proteins
  • multidrug resistance-associated protein 2