Multidrug-resistant genotype (ABCB1) and seizure recurrence in newly treated epilepsy: data from international pharmacogenetic cohorts.
OBJECTIVE
The association between a specific polymorphism (3435C>T) in the ABCB1 gene, coding for the membrane drug transporter P-glycoprotein (PgP), and pharmacoresistance to seizure control is controversial. Studies have been limited by multiple drug use, chronic cohorts with varying definitions, and retrospective clinical data. Herein we examine the relationship of this polymorphism with seizure recurrence in three independent international cohorts of patients newly treated for epilepsy.


METHODS
Data were collected on demographics, medication details, and seizure control after 12  months of treatment. The distribution of ABCB1 3435C>T genotypes was compared between patients with and without recurrent unprovoked seizures.


RESULTS
Five hundred forty-two newly treated patients were enrolled (212 from Australia, 285 from Scotland, and 45 from Hong Kong). A total of 38.4% had recurrent unprovoked seizures after starting antiepileptic drug (AED) treatment. Genotype frequencies and ethnicity did not differ between the Scottish and Australian cohorts, but both were significantly different in the Hong Kong cohort. There was no significant relationship between the ABCB1 3435C>T genotype and the rate of recurrence of unprovoked seizures in the three cohorts individually or combined; however the epilepsy syndrome and a greater number of seizures pretreatment was associated with an increased risk of seizure recurrence.


CONCLUSIONS
The ABCB1 3435C>T genotype does not have a major role in determining the efficacy of seizure control with initial AED therapy. The study highlights issues that arise in combining pharmacogenetic datasets from different ethnic regions and health systems, an approach that is essential to advance this field.
Szoeke
Cassandra
C
Departmentof Neurology, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia.
Sills
Graeme J
GJ
Kwan
Patrick
P
Petrovski
Slave
S
Newton
Mark
M
Hitiris
Nikolas
N
Baum
Larry
L
Berkovic
Samuel F
SF
Brodie
Martin J
MJ
Sheffield
Leslie J
LJ
O'Brien
Terence J
TJ
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D001315:Australia / Q000208:ethnology; D015331:Cohort Studies; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004827:Epilepsy / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006723:Hong Kong / Q000208:ethnology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012008:Recurrence; D012606:Scotland / Q000208:ethnology; D044465:White People / Q000235:genetics
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants