title: Detection of the four sequence variations of MDR1 gene using TaqMan MGB probe based real-time PCR and haplotype analysis in healthy Japanese subjects.
abstract: OBJECTIVE
  P-glycoprotein (P-gp) is significant from the viewpoint of pharmacokinetics/pharmacodynamics (PK/PD). MDR1 gene encodes P-gp and has a wide variety of SNPs. As the SNPs may be one of the factors that induce pharmacogenetic individual difference, haplotype analysis is necessary to evaluate the PK/PD.
  
  
  METHODS
  The SNPs of the detected MDR1 were -129T>C, 325G>A, 2677G>T/A, and 3435C>T. For the analysis of linkage disequilibrium (LD) and haplotype analysis, and for the reconstruction of the haplotype pair, ARLEQUIN and PHASE were employed.
  
  
  RESULTS
  The result of the chi(2) test detected significant LD between -129 and 2677, -129 and 3435, and 2677 and 3435. There were 9 haplotypes: T-G-C, T-T-C, C-T-C, T-A-C, C-A-C, T-G-T, T-T-T, C-G-T, and C-T-T.
  
  
  CONCLUSIONS
  LD was found among the positions -129, 2677 and 3435. As a result, 9 haplotypes exists in the Japanese population. These results suggest that it would be necessary to give consideration to haplotype for the purpose of evaluating the PK/PD of the drugs transported by P-gp.
authors.affiliation: Division of Pharmaceutical Health Care and Sciences, Sapporo Medical University, South 1, West 16, Chuo-ku, Sapporo, 060-8543 Japan. ksaitoh@sapmed.ac.jp
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Saito
authors.forename: Sachie
authors.initials: S
authors.lastname: Miyake
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Moriya
authors.forename: Miyuki
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Fumio
authors.initials: F
authors.lastname: Itoh
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
authors.forename: Nahoko
authors.initials: N
authors.lastname: Kurosawa
authors.forename: Eiji
authors.initials: E
authors.lastname: Owada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyamoto
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015342:DNA Probes / Q000235:genetics*; D005091:Exons / Q000235:genetics; D019450:Genes, MDR / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006262:Health; D006579:Heterozygote; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000295:instrumentation / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019914:Taq Polymerase / Q000378:metabolism
chemical_list: D017931:DNA Primers; D015342:DNA Probes; D019914:Taq Polymerase