Polymorphism of the MDR1/ABCB1 C3435T drug-transporter and resistance to anticonvulsant drugs: a meta-analysis.
BACKGROUND
Approximately one-third of patients with epilepsy patients have recurrent seizures despite therapy. It has been suggested that therapeutic failure is associated with high expression of the multidrug efflux ABCB1 (MDR1) drug-transporter; specifically, that patients with the 3435CC genotype have higher efflux of anticonvulsants out of brain tissue, with correspondingly lower concentrations in the central nervous system.


METHODS
We conducted a meta-analysis to examine the association between MDR1 polymorphisms and the response to anticonvulsants. We included all published studies until September 2007, in which patients with responsive and unresponsive seizure disorders underwent genotyping for ABCB1 C3435T. Individual and summary odds ratios were calculated using a random effects model. A secondary analysis was also performed, stratifying the studies by their ethnic distribution to account for genetic heterogeneity. We also performed a cumulative analysis by date of publication for the included studies using a random effects model.


RESULTS
We identified 11 case-control studies involving 3,371 patients (1,646 patients with drug-resistant epilepsy and 1,725 controls). We identified no significant association between anticonvulsant drug resistance and MDR1 polymorphism [odds ratio 1.15; 95% confidence interval (CI) 0.78-1.70; p = 0.48). Subanalysis of studies according to ethnicity yielded similar findings [European cohort: OR = 1.31; 95% CI 0.89-1.94, p = 0.18; Asian cohort: OR = 0.99; 95% CI 0.51-1.89, p = 0.96).


CONCLUSIONS
We found no association between ABCB1 genotype and response to anticonvulsant drugs. At the present time, genetic typing for MDR1 polymorphism is not warranted for patients with drug-resistant epilepsy.
Bournissen
Facundo Garcia
FG
Divisions of Clinical Pharmacology and Toxicology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Moretti
Myla E
ME
Juurlink
David N
DN
Koren
Gideon
G
Walker
Mugabe
M
Finkelstein
Yaron
Y
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000927:Anticonvulsants / Q000627:therapeutic use*; D016022:Case-Control Studies; D016001:Confidence Intervals; D003431:Cross-Cultural Comparison; D016208:Databases, Factual / Q000706:statistics & numerical data; D004351:Drug Resistance / Q000235:genetics*; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants