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CYP3A5 GENETIC POLYMORPHISMS IN DIFFERENT ETHNIC POPULATIONS

Jean-Nicholas Roy, Julie Lajoie, Lynn S. Zijenah, Azemi Barama, Charles Poirier, Brian J. Ward and Michel Roger
Drug Metabolism and Disposition July 2005, 33 (7) 884-887; DOI: https://doi.org/10.1124/dmd.105.003822
Jean-Nicholas Roy
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Julie Lajoie
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Lynn S. Zijenah
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Azemi Barama
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Charles Poirier
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Brian J. Ward
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Michel Roger
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Abstract

Cyp3A5 activity varies within any given ethnic population, suggesting that genetic variation within the Cyp3A5 gene may be the most important contributor to interindividual and interracial differences in Cyp3A-dependent drug clearance and response. The full extent of Cyp3A5 polymorphism in a white and an indigenous African population was analyzed using DNA direct sequencing procedures. The presence of 10 and 12 single nucleotide polymorphisms was detected in the white and African samples, respectively. Thirteen novel mutations occurring at low frequencies were identified in these populations. Significant differences were observed in the distribution of Cyp3A5*3, Cyp3A5*6, and Cyp3A5*7 alleles among white and African populations. The frequency of Cyp3A5*3 allele in white Canadians (∼93%) is higher than in Zimbabweans (77.6%) (p < 0.001). In contrast, Cyp3A5*6 and Cyp3A5*7 alleles are relatively frequent in African subjects (10–22%) but absent in white subjects (p < 0.001). These differences may reflect evolutionary pressures generated by environmental factors in geographically distinct regions. However, the genetic polymorphism of Cyp3A5 alone does not explain the interindividual differences in Cyp3A-mediated metabolism.

Footnotes

  • This work was supported by a grant from the Réseau Sida et maladies infectieuses du Fonds de la Recherche en Santé du Québec (FRSQ). M. Roger is supported by a career award from FRSQ. The ZVITAMBO project is supported by the Canadian International Development Agency (R/C Project 690/M3688), Cooperative Agreement DAN 0045-A-005094-00 between the U.S. Agency for International Development and The Johns Hopkins University School of Hygiene and Public Health, and the Rockefeller Foundation. It is a collaborative project of The University of Zimbabwe, The Harare City Health Department, The Johns Hopkins University School of Hygiene and Public Health, and the Montreal General Hospital Research Institute, McGill University.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.105.003822.

  • ABBREVIATIONS: PCR, polymerase chain reaction; A-RFLP, amplified restriction fragment length polymorphism; SNP, single nucleotide polymorphism.

    • Received February 1, 2005.
    • Accepted April 12, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 33 (7)
Drug Metabolism and Disposition
Vol. 33, Issue 7
1 Jul 2005
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OtherShort Communication

CYP3A5 GENETIC POLYMORPHISMS IN DIFFERENT ETHNIC POPULATIONS

Jean-Nicholas Roy, Julie Lajoie, Lynn S. Zijenah, Azemi Barama, Charles Poirier, Brian J. Ward and Michel Roger
Drug Metabolism and Disposition July 1, 2005, 33 (7) 884-887; DOI: https://doi.org/10.1124/dmd.105.003822

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OtherShort Communication

CYP3A5 GENETIC POLYMORPHISMS IN DIFFERENT ETHNIC POPULATIONS

Jean-Nicholas Roy, Julie Lajoie, Lynn S. Zijenah, Azemi Barama, Charles Poirier, Brian J. Ward and Michel Roger
Drug Metabolism and Disposition July 1, 2005, 33 (7) 884-887; DOI: https://doi.org/10.1124/dmd.105.003822
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