title: Complex haplotypic effects of the ABCB1 gene on epilepsy treatment response.
abstract: OBJECTIVE
  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.
  
  
  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]).
  
  
  CONCLUSIONS
  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.
authors: National Taiwan University Hospital and College of Medicine, NTU, Department of Pharmacology, 1 Jen-Ai Road, Section 1, Taipei, Taiwan 100.
authors: Chin-Chuan
authors: CC
authors: Hung
authors: John Jen
authors: JJ
authors: Tai
authors: Chun-Jung
authors: CJ
authors: Lin
authors: Ming-Jen
authors: MJ
authors: Lee
authors: Horng-Huei
authors: HH
authors: Liou
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000483:Alleles; D000927:Anticonvulsants / Q000627:therapeutic use*; D004351:Drug Resistance; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics*; D005091:Exons; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics / Q000502:physiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants