Detection of the four sequence variations of MDR1 gene using TaqMan® MGB probe based real-time PCR and haplotype analysis in healthy Japanese subjects

Objectives 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. Design and 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 χ2 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.