Complex haplotypic effects of the ABCB1 gene on epilepsy treatment response
Journal
Pharmacogenomics
Journal Volume
6
Journal Issue
4
Pages
411
Date Issued
2005-06
Author(s)
Abstract
Objectives: The aim of this study was to investigate the association of the complex haplotype system of the adenosine triphosphate-binding cassette B1 (ABCB1) gene with the epilepsy treatment response. Methods and results: Ten polymorphisms were genotyped in 108 drug-resistant epileptic patients, 223 seizure-free patients and 287 normal controls. Highly significant linkage disequilibrium was shown among exon 12 C1236T, exon 21 G2677T and exon 26 C3435T. Haplotypic analysis demonstrated that patients with the CGC, TGC, and TTT haplotypes were more likely to be drug resistant. Further analysis of haplotype combinations demonstrated that drug-resistant patients tended to have the CGC/CGC, CGC/TGC, CGC/TTT, and TGC/TTT haplotype combinations over the seizure-free patients and controls (all p-values < 0.0001). In contrast, patients with the TTC/TTC, TTC/CGT, TTC/TGT, CGT/CGT and TGT/CGT haplotype combinations were more likely to be seizure-free (all p-values < 0.0001 except CGT/CGT [p = 0.0063]). Conclusion: Our results showed that the three loci, C1236T, G2677T and C3435T, jointly influenced the treatment response for epileptic patients. They should be regarded together as a complex polymorphic drug-response system. These findings suggest that examination of the haplotypes of the three loci could be useful in predicting drug resistance in epilepsy. ? 2005 Future Medicine Ltd.
SDGs
Other Subjects
ABC transporter; anticonvulsive agent; multidrug resistance protein 1; unclassified drug; adult; article; controlled study; disease classification; drug response; epilepsy; exon; female; gene linkage disequilibrium; gene locus; genetic polymorphism; haplotype; human; major clinical study; male; restriction fragment length polymorphism; single nucleotide polymorphism; statistical analysis; statistical significance; Adult; Alleles; Anticonvulsants; Drug Resistance; Epilepsy; Exons; Female; Genotype; Haplotypes; Humans; Linkage Disequilibrium; Male; Middle Aged; P-Glycoprotein; Polymorphism, Single Nucleotide; Taiwan
Type
journal article