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Single nucleotide polymorphisms of ABCB1 (MDR1) gene and distinct haplotype profile in a West Black African population

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

The ABCB1 (MDR1) multidrug transporter plays a key role in determining drug bioavailability. Differences in drug response exist among different ethnic groups. However, until now, no haplotype data are available in a Black African population.

Methods

Exons 2, 7, 10, 11, 12, 14, 17, 21, 26, and the surrounding intronic regions were sequenced using genomic DNA from 111 Beninese subjects to examine 19 intragenic single nucleotide polymorphisms (SNPs). Linkage disequilibrium analysis and haplotypes were generated using the expectation–maximization algorithm.

Results

We identified 12 SNPs, 3 of which were novel: IVS9-57delA, IVS9-8T>A, 1662G>C (exon 14). The most common SNP was IVS14+38A>G. At the MRD1 locus, 53 haplotypes were inferred from the SNP data sets. The 4 SNPs, IVS6+139C>T, IVS9-44A>G, 1236C>T, and 3435C>T, showed strong linkage disequilibrium with each other, confirming the block concept. Moreover, our findings suggest that ABCB1 exonic SNPs are less frequently observed in our population than in African-Americans.

Conclusion

Our data are compatible with a close evolutionary relationship in Black Africans from Benin.

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References

  1. Ameyaw MM, Regateiro F, Li T, Liu X, Tariq M, Mobarek A, Thomton N, Folayan GO, Githang’a J, Indalo A, Ofori-Adjei D, Price-Evans DA, McLeod HL (2001) MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics 11:217–221

    Article  CAS  PubMed  Google Scholar 

  2. Cascorbi I, Gerloff T, Johne A, Meisel C, Hoffmeyer S, Schwab M, Schaeffeler E, Eichelbaum M, Brinkmann U, Roots I (2001) Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin Pharmacol Ther 69:169–174

    Article  CAS  PubMed  Google Scholar 

  3. Fellay J, Marzolini C, Meaden ER, Back DJ, Buclin T, Chave JP, Decosterd L, Furrer H, Opravil M, Pantaleo G et al (2002) Response to antiretroviral treatment in HIV-1 infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet 359:30–36

    Article  Google Scholar 

  4. Fromm MF (2002) Influence of MDR1 polymorphisms on P-glycoprotein expression and function in humans. Adv Drug Deliv Rev 54:1295–1310

    Article  CAS  PubMed  Google Scholar 

  5. Gottesman MM, Pastan I, Ambudkar SV (1996) P-glycoprotein and multidrug resistance. Curr Opin Genet Dev 6:610–617

    Article  Google Scholar 

  6. Hitzl M, Drescher S, van der Kuip H, Schaffeler E, Fischer J, Schwab M, Eichelbaum M, Fromm MF (2001) The C3435T mutation in the human MDR1 gene is associated with altered efflux of the P-glycoprotein substrate rhodamine 123 from CD56+ natural killer cells. Pharmacogenetics 11:293–298

    Article  Google Scholar 

  7. Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmoller J, Johne A, Cascorbi I, Gerloff T, Roots I, Eichelbaum M, Brinkmann U (2000) Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A 97:3473–3478

    Article  CAS  PubMed  Google Scholar 

  8. Ito S, Ieiri I, Tanabe M, Suzuki A, Higuchi S, Otsubo K (2001) Polymorphisms of the ABC transporter genes, MDR1, MRP1 and MR2P/cMOAT, in healthy Japanese subjects. Pharmacogenetics 11:175–184

    Article  Google Scholar 

  9. Johne A, Kopke K, Gerloff T, Mai I, Rietbrock S, Meisel C, Hoffmeyer S, Kerb R, Fromm MF, Brinkmann U, Eichelbaum M, Brockmoller J, Cascorbi I, Roots I (2002) Modulation of steady-state kinetics of digoxin by haplotypes of the P-glycoprotein MDR1 gene. Clin Pharmacol Ther 72:584–594

    Article  Google Scholar 

  10. Kim RB, Leake BF, Choo EF, Dresser GK, Kubba SV, Schwarz UI, Taylor A, Xie HG, McKinsey J, Zhou S, Lan LB, Schuetz JD, Schuetz EG, Wilkinson GR (2001) Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin Pharmacol Ther 70:189–199

    Article  CAS  PubMed  Google Scholar 

  11. Kroetz DL, Pauli-Magnus C, Hodges LM, Huang CC, Kawamoto M, Johns SJ, Stryke D, Ferrin TE, DeYoung J, Taylor T, Carlson EJ, Herskowitz I, Giacomini KM, Clark GA (2003) Sequence diversity and haplotype structure in the human ABCB1 (MDR1, multidrug resistance transporter) gene. Pharmacogenetics 13:481–494

    Article  CAS  PubMed  Google Scholar 

  12. Nakamura T, Sakaeda T, Horinouchi M, Tamura T, Aoyama N, Shirakawa T et al (2002) Effect of the mutation (C3435T) at exon 26 of the MDR1 gene on expression level of MDR1 messenger ribonucleic acid in duodenal enterocytes of healthy Japanese subjects. Clin Pharmacol Ther 71:297–303

    Article  Google Scholar 

  13. Sai K, Kaniwa N, Itoda M, Saito Y, Hasegawa R, Komamura K, Ueno K, Kamakura S, Kitakaze M, Shirao K, Minami H, Ohtsu A, Yoshida T, Saijo N, Kitamura Y, Kamatani N, Ozawa S, Sawada J (2003) Haplotype analysis of ABCB1/MDR1 blocks in a Japanese population reveals genotype-dependent renal clearance of irinotecan. Pharmacogenetics 13:741–757

    Article  Google Scholar 

  14. Sakaeda T, Nakamura T, Horinouchi M, Kakumoto M, Ohmoto N, Sakai T, Morita Y, Tamura T, Aoyama N, Hirai M, Kasuga M, Okumura K (2001) MDR1 genotype- related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects. Pharm Res 18:1400–1404

    Article  CAS  PubMed  Google Scholar 

  15. Sakaeda T, Nakamura T, Okumura K (2002) MDR1 genotype-related pharmacokinetics and pharmacodynamics. Biol Pharm Bull 25:1391–1400

    Article  Google Scholar 

  16. Sakaeda T, Nakamura T, Okumura K (2003) Pharmacogenetics of MDR1 and its impact on the pharmacokinetics and pharmacodynamics of drugs. Pharmacogenomics 4:397–410

    Article  Google Scholar 

  17. Schaeffeler E, Eichelbaum M, Brinkmann U, Penger A, Asante-Poku S, Zanger UM, Schwab M (2001) Frequency of C3435T polymorphism of MDR1 gene in African people. Lancet 358:383–384

    Article  Google Scholar 

  18. Tajima F (1989) Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123:585–595

    CAS  PubMed  Google Scholar 

  19. Tanabe M, Ieiri I, Nagata N, Inoue K, Ito S, Kanamori Y, Takahashi M, Kurata Y, Kigawa J, Higuchi S, Terakawa N, Otsubo K (2001) 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

    CAS  PubMed  Google Scholar 

  20. Tang K, Ngoi SM, Gwee PC, Chua JM, Lee EJ, Chong SS, Lee CG (2002) Distinct haplotype profiles and strong linkage disequilibrium at the MDR1 multidrug transporter gene locus in three ethnic Asian populations. Pharmacogenetics 12:437–450

    Article  CAS  PubMed  Google Scholar 

  21. Tang K, Wong LP, Lee EJ, Chong SS, Lee CG (2004) Genomic evidence for recent positive selection at the human MDR1 gene locus. Hum Mol Genet 13:783–797

    Article  Google Scholar 

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Acknowledgements

We would like to thank Michel Heusterspreute and Vital Ekanmian for their helpful technical assistance. This study was supported by the Islamic Development Bank and Walloon Region (Waleo 2002, Grant n. 215131/0938840). None of the authors claims any conflict of interest.

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Correspondence to Jean-Luc Gala.

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Allabi, A.C., Horsmans, Y., Issaoui, B. et al. 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). https://doi.org/10.1007/s00228-004-0879-0

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  • DOI: https://doi.org/10.1007/s00228-004-0879-0

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