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Analyses of Single Nucleotide Polymorphisms and Haplotype Linkage of the Human ABCB1 (MDR1) Gene in Korean  

Ryu, Ho-Cheol (College of Pharmacy, SungKyunKwan University)
Kwon, Hyog-Young (College of Pharmacy, SungKyunKwan University)
Choi, Il-Kuen (Choi's Clinic)
Rhee, Dong-Kwon (College of Pharmacy, SungKyunKwan University)
Publication Information
Archives of Pharmacal Research / v.29, no.12, 2006 , pp. 1132-1139 More about this Journal
Abstract
Single nucleotide polymorph isms (SNPs) in the MDR1 gene that are responsible for drug efflux can cause toxicity. Therefore, this study determined the SNPs of the Korean MDR1 gene, and analyzed the haplotypes and a linkage disequilibrium (LD) of the SNPs determined. The frequency of 9 SNPs from the MDR1 gene was determined by PCR-RFLP analyses of 100 to 500 healthy individuals. The frequcies of the SNPs were C3435T (47.7%), G2677T (37.6%), G2677A (4.4%), T1236C (21.7%), T129C (8%), A2956G (2.5%), T307C (1.5%), A41aG (9.2%), C145G (0%), and G4030C (0%). Analyses of the haplotype structure and an estimation of the LD of the combined polymorph isms demonstrated that the frequency of the 1236T-2677G-3435T haplotype is much higher in Koreans (14.1%) than in Chinese and western black Africans and the C3435T SNP in Koreans appears to have LD with T129C in Koreans for the first time. These results provide insight into the genetic variation of MDR1 in Koreans, and demonstrated the possibility of a new LD in this gene.
Keywords
ABCB1; Korean; SNP; Haplotype; Linkage disequilibrium;
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1 Brenner, S. S. and Klotz, U., P-glycoprotein function in the elderly. Eur. J. Clin. Pharmacol., 60, 97-102 (2004)   DOI
2 Gottesman, M. M. and Pastan, I., Biochemistry of multidrug resistance mediated by the multidrug transpoter. Annu. Rev. Biochem., 62, 385-427 (1993)   DOI   ScienceOn
3 Hoffmeyer, S., Burk, O., von Richter, O., Arnold, H. P., Brockmoller, J., Johne, A., Cascorbi, I., Gerloff, T., Roots, I., Eichelbaum, M., and Brinkmann, U., Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with Pglycoprotein expression and activity in vivo. Proc. Natl. Acad. Sci. U.S.A., 97, 3473-3478 (2000)
4 Illmer, T., Schuler, U. S., Thiede, C., Schwarz, U. I., Kim, R. B., Gotthard, S., Freund, D., Schakel, U., Ehninger, G., and Schaich, M., MDR1 gene polymorphisms affect therapy outcome in acute myeloid leukemia patients. Cancer Res., 62, 4955-4962 (2002)
5 Kioka, N., Tsubota, J., Kakehi, Y., Komano, T., Gottesman, M. M., Pastan, I., and Ueda, K., P-glycoprotein gene (MDR1) cDNA from human adrenal: normal P-glycoprotein carries Gly185 with an altered pattern of multidrug resistance. Biochem. Biophys. Res. Commun., 162, 224-231 (1989)   DOI   ScienceOn
6 Yamauchi, A., Ieiri, I., Kataoka, Y., Tanabe, M., Nishizaki, T., Oishi, R., Higuchi, S., Otsubo, K., and Sugimachi, K., Neurotoxicity induced by tacrolimus after liver transplantation: relation to genetic polymorphisms of the ABCB1 (MDR1) gene. Transplantation, 74, 571-572 (2002)   DOI   ScienceOn
7 Zhang, W. X., Chen, G. L., Zhang, W., Tan, Z. R., Liu, J., Zhou, G., Hu, D. L., and Zhou, H. H., MDR1 genotype do not influence the absorption of a single oral dose of 100 mg talinolol in healthy Chinese males. Clin. Chim. Acta, 359, 46- 52 (2005)   DOI   ScienceOn
8 Gerloff, T., Schaefer, M., Johne, A., Oselin, K., Meisel, C., Cascorbi, I., and Roots, I., MDR1 genotypes do not influence the absorption of a single oral dose of 1 mg digoxin in healthy white males. Br. J. Clin. Pharmacol., 54, 610-616 (2002)   DOI   ScienceOn
9 Kim, R. B., Leake, B. F., Choo, E. F., Dresser, G. K., Kubba, S. V., Schwarz, U. I., Taylor, A., Xie, H. G., McKinsey, J., Zhou, S., Lan, L. B., Schuetz, J. D., Schuetz, E. G., and Wilkinson, G. R., Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin. Pharmacol. Ther., 70, 189-199 (2001)   DOI   ScienceOn
10 Balram, C., Sharma, A., Sivathasan, C., and Lee, E. J. D., Frequency of C3435T single nucleotide MDR1 genetic polymorphism in an Asian population: phenotypicgenotypic correlates. Br. J. Clin. Pharmacol., 56, 78-83 (2003)   DOI   ScienceOn
11 Marzolini, C., Paus, E., Buclin, T., and Kim, R. B., Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin. Pharmacol. Ther., 75, 13-33. (2004)   DOI   ScienceOn
12 Schaeffeler, E., Eichelbaum, M., Brinkmann, U., Penger, A., Asante-Poku, S., Zanger, U. M., and Schwab, M., Frequency of C3435T polymorphism of MDR1 gene in African people. Lancet, 358, 383-384 (2001)   DOI   ScienceOn
13 Chowbay, B., Cumaraswamy, S., Cheung, Y. B., Zhou, Q., and Lee, E. J., Genetic polymorphisms in MDR1 and CYP3A4 genes in Asians and the influence of MDR1 haplotypes on cyclosporin disposition in heart transplant recipients. Pharmacogenetics, 13, 89-95 (2003)   DOI
14 Tanabe, M., Ieiri, I., Nagata, N., Inoue, K., Ito, S., Kanamori, Y., Takahashi, M., Kurata, Y., Kigawa, J., Higuchi, S., Terakawa, N., and Otsubo, K., Expression of P-glycoprotein in human placenta: relation to genetic polymorphism of the multidrug resistance (MDR)-1 gene. J. Pharmacol. Exp. Ther., 297, 1137-1143 (2001)
15 Shon, J. H., Yoon, Y. R., Hong, W. S., Nguyen, P. M., Lee, S. S., Choi, Y. G., Cha, I. J., and Shin, J. G., Effect of itraconazole on the pharmacokinetics and pharmacodynamics of fexofenadine in relation to the MDR1 genetic polymorphism. Clin. Pharmacol. Ther., 78, 191-201 (2005)   DOI   ScienceOn
16 Sigsmund, M., Brinkmann, U., Schaffeler, E., Weirich, G., Schwab, M., Eichelbaum, M., Fritz, P., Burk, O., Decker, J., Alken, P., Rothenpieler, U., Kerb, R., Hoffmeyer, S., and Brauch, H., Association of the P-glycoprotein transporter MDR1 (C3435T) polymorphism with the susceptibility to renal epithelial tumors. J. Am. Soc. Nephrol., 13, 1847-1854 (2002)   DOI   ScienceOn
17 Goto, M., Masuda, S., Saito, H., Uemoto, S., Kiuchi, T., Tanaka, K., and Inui, K., C3435T polymorphism in the MDR1 gene affects the enterocyte expression level of CYP3A4 rather than Pgp in recipients of living-donor liver transplantation. Pharmacogenetics, 12, 451-457. (2002)   DOI
18 Cascorbi, I., Gerloff, T., Johne, A., Meisel, C., Hoffmeyer, S., Schwab, M., Schaeffeler, E., Eichelbaum, M., Brinkmann, U., and Roots, I., Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin. Pharmacol. Ther., 69, 169-174 (2001)   DOI   ScienceOn
19 Jung, H. Y., Park, J. S., Park, Y. J., Kim, Y. J., Kim, K., and Koh, I. S., HapAnalyzer: Minimum haplotype analysis system for association studies. Genomics Informatics, 2, 107-109. (2004)
20 Kroetz, D. L., Pauli-Magnus, C., Hodges, L. M., Huang, C. C., Kawamoto, M., Johns, S. J., Stryke, D., Ferrin, T. E., DeYoung, J., Taylor, T., Carlson, E. J., Herskowitz, I., Giacomini, K. M., and Clark, G. A., Sequence diversity and haplotype structure in the human ABCB1 (MDR1, multidrug resistance transporter) gene. Pharmacogenetics, 13, 481-494 (2003)   DOI
21 Schwab, D., Fischer, H., Tabatabaei, A., Poli, S., and Huwyer, J., Comparison of in vitro P-glycoprotein screening assay: recommendations for their use in drug discovery. J. Med. Chem., 46, 1716-1725 (2003)   DOI   ScienceOn
22 Yi, S. Y., Hong, K. S., Lim, H. S., Chung, J. Y., Oh, D. S., Kim, J. R., Jung, H. R., Cho, J. Y., Yu, K. S., Jang, I. J., and Shin, S. G., A variant 2677A allele of the MDR1 gene affects fexofenadine disposition. Clin. Pharmacol. Ther., 76, 418-427 (2004)   DOI   ScienceOn
23 Ito, S., Ieiri, I., Tanabe, M., Suzuki, A., Higuchi, S., and Otsubo, K., Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in healthy Japanese subjects. Pharmacogenetics, 11, 175-184 (2001)   DOI
24 Tang, K., Ngoi, S. M., Gwee, P. C., Chua, J. M., Lee, E. J., Chong, S. S., and Lee, C. G., Distinct haplotype profiles and strong linkage disequilibrium at the MDR1 multidrug transporter gene locus in three ethnic Asian populations. Pharmacogenetics, 12, 437-450 (2002)   DOI
25 Ameyaw, M. M., Regateiro, F., Li, T., Liu, X., Tariq, M., Mobarek, A., Thornton, N., Folyayan, G. O., Githang'a, J., Indalo, A., Ofori-Adjei, D., Price-Evans, D. A., and McLeod, H. L., MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics, 11, 217–221 (2001)   DOI   ScienceOn
26 Allabi, A. C., Horsmans, Y., Issaoui, B., and Gala, J. L., Single nucleotide polymorphisms of ABCB1 (MDR1) gene and distinct haplotype profile in a West Black African population. Eur. J. Clin. Pharmacol., 61, 97-102 (2005)   DOI