Linked Life Data

17125969

Source:http://linkedlifedata.com/resource/pubmed/id/17125969

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-2-19
pubmed:abstractText
Controversy has surrounded the reported association of the single nucleotide polymorphism (SNP) C3435T of the ATP-binding cassette subfamily B member 1 (ABCB1, MDR1) gene, with refractory epilepsy. Here we examine this question by: (1) attempting to replicate the original association, (2) assessing the association of other variants in high linkage disequilibrium (LD) with C3435T, and (3) evaluating and comparing our findings with other published studies. We defined drug-responsiveness as seizure freedom or a 50% or more reduction in seizure frequency in the preceding year. Drug resistance was defined as a less than 50% reduction in seizure frequency in the preceding year. We used a combination of map-based (tagging SNPs) and direct sequence-based methods allowing a comprehensive assessment of variation across the associated interval. Genotypic data on 8 SNPs was collected on 440 patients, of whom 242 were drug-responsive and 198 were drug-resistant. We were unable to observe the original association of drug-resistant epilepsy with C3435T, nor any association with other functional variants at SNP or haplotype level in the ABCB1 gene. Evaluation of other attempted replication studies suggest that if the original C3435T association is indeed real, it would appear highly sensitive to the phenotype used. Alternatively, the discrepant results of this and other association attempts may be indicative of the original report of the CC genotype at C3435T in ABCB1 being a false positive finding. Variability in phenotypic descriptions in genetic association studies may partly explain the inconsistency of attempted replications.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0920-1211
pubmed:author
pubmed:issnType
Print
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
192-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
The controversial association of ABCB1 polymorphisms in refractory epilepsy: an analysis of multiple SNPs in an Irish population.
pubmed:affiliation
Department of Clinical Neurological Sciences, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't