Aims: 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.
Materials And 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.
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http://dx.doi.org/10.1089/gtmb.2013.0362 | DOI Listing |
Onco Targets Ther
February 2020
Department of Pharmacy, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei 441021, People's Republic of China.
Objective: Multidrug resistance-associated protein 2 (MRP2), encoded by gene, is involved in the efflux of certain anticancer drugs. Here we observed whether the (G1249A) polymorphism impacts the transport abilities of MRP2-dependent paclitaxel, docetaxel, and doxorubicin in recombinant LLC-PK1 cell lines.
Methods: LLC-PK1 cell lines transfected with wild-type and variant alleles were used to evaluate the sensitivity, intracellular accumulation, and transmembrane transport of paclitaxel, docetaxel, and doxorubicin.
Clin Drug Investig
November 2018
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada.
Background And Objectives: The hematological side effects associated with mycophenolic acid (MPA) are relatively common and have severe consequences. The majority of literature data have not shown clear consistency in the MPA exposure-neutropenia relationship. We hypothesized that (i) adult de novo kidney transplant recipients who develop neutropenia have relatively higher dose-normalized MPA exposure than patients without neutropenia, and (ii) the observed neutropenia may be explained by polymorphisms in metabolism and/or transporter genes responsible for MPA disposition.
View Article and Find Full Text PDFPharm Res
August 2017
Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, 170 Frelinghuysen Road, Piscataway, New Jersey, 08854, USA.
Purpose: Multidrug resistance-associated protein 2 (MRP2/ABCC2) is an efflux pump that removes drugs and chemicals from cells. We sought to characterize the expression, trafficking and in vitro activity of seven single nucleotide polymorphisms (SNPs) in the ABCC2 gene.
Methods: ABCC2 SNPs were generated using site-directed mutagenesis and stably expressed in Flp-In HEK293 cells, which allows targeted insertion of transgenes within the genome.
Epilepsy Res
May 2015
Department of Biological Science and Biotechnology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, PR China. Electronic address:
ABCC2 gene polymorphisms have been shown to be associated with drug-resistant epilepsy. However, the published results were controversial. To comprehensively re-evaluate the association between ABCC2 gene polymorphisms and drug-resistant epilepsy in Asian, we carried out this meta-analysis, which included eight related studies.
View Article and Find Full Text PDFGenet Test Mol Biomarkers
February 2014
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China .
Aims: 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.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!