Detection of the four sequence variations of MDR1 gene using TaqMan MGB probe based real-time PCR and haplotype analysis in healthy Japanese subjects.
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.
Saito
Katsuhiko
K
Division of Pharmaceutical Health Care and Sciences, Sapporo Medical University, South 1, West 16, Chuo-ku, Sapporo, 060-8543 Japan. ksaitoh@sapmed.ac.jp
Miyake
Sachie
S
Moriya
Hiroyuki
H
Yamazaki
Miyuki
M
Itoh
Fumio
F
Imai
Kohzoh
K
Kurosawa
Nahoko
N
Owada
Eiji
E
Miyamoto
Atsushi
A
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
D017931:DNA Primers; D015342:DNA Probes; D019914:Taq Polymerase