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Pharmacogenomics of CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and MDR1 in Vietnam

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

Abstract

Aim

The aim of this study was to obtain pharmacogenetic data in a Vietnamese population on genes coding for proteins involved in the elimination of drugs currently used for the treatment of malaria and human immunodeficiency virus/acquired immunodeficiency syndrome.

Method

The main polymorphisms on the cytochrome P450 (CYP) genes, CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4 and CYP3A5, and the multi-drug resistance 1 gene (MDR1) were genotyped in 78 healthy Vietnamese subjects. Pharmacokinetic metrics were available for CYP2A6 (coumarin), CYP2C19 (mephenytoin), CYP2D6 (metoprolol) and CYP3As (midazolam), allowing correlations with the determined genotype.

Results

In the CYP2 family, we detected alleles CYP2A6*4 (12%) and *5 (15%); CYP2B6*4 (8%), *6 (27%); CYP2C19*2 (31%) and *3 (6%); CYP2D6*4, *5, *10 (1, 8 and 44%, respectively). In the CYP3A family, CYP3A4*1B was detected at a low frequency (2%), whereas CYP3A5 *3 was detected at a frequency of 67%. The MDR1 3435T allele was present with a prevalence of 40%. Allele proportions in our cohort were compared with those reported for other Asian populations. CYP2C19 genotypes were associated to the S-4′-OH-mephenytoin/S-mephenytoin ratio quantified in plasma 4 h after intake of 100 mg mephenytoin. While CYP2D6 genotypes were partially reflected by the α-OH-metroprolol/metoprolol ratio in plasma 4 h after dosing, no correlation existed between midazolam plasma concentrations 4 h post-dose and CYP3A genotypes.

Conclusions

The Vietnamese subjects of our study cohort presented allele prevalences in drug-metabolising enzymes that were generally comparable with those reported in other Asian populations. Deviations were found for CYP2A6*4 compared to a Chinese population (12 vs. 5%, respectively; P = 0.023), CYP2A6*5 compared with a Korean population (15 vs. <1%, respectively; P < 0.0001), a Malaysian population (1%; P < 0.0001) and a Chinese population (1%; P < 0.0001); CYP2B6*6 compared with a Korean population (27 vs. 12%; P = 0.002) and a Japanese population (16%; P = 0.021). Pharmacokinetic metrics versus genotype analysis reinforces the view that the predictive value of certain globally common variants (e.g. CYP2D6 single nucleotide polymorphisms) should be evaluated in a population-specific manner.

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Acknowledgements

Veiga MI, Ferreira PE and Cavaco I are recipients of Fundacão para a Ciência e Tecnologia, Portugal, PhD Grant (SFRH/BD/28393/2006, SFRH/BD/28368/2006 and SFRH/BD/8887/2002, respectively). This work was supported in part by the Swedish International Development Cooperation Agency (SIDA/SAREC).

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Authors and Affiliations

  1. Malaria Research, Unit of Infectious Diseases, Department of Medicine, Karolinska Institute, Scheele Lab B2, Retzius väg 10:05, 17177, Stockholm, Sweden

    M. I. Veiga, P. E. Ferreira, A. Björkman & J. P. Gil

  2. Unit for Pharmacokinetics and Drug Metabolism, Section for Pharmacology, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden

    S. Asimus & M. Ashton

  3. Centre of Molecular and Structural Biomedicine (CBME)/Institute of Biotechnology and Bioengineering (IBB), University of Algarve, Gambelas, Portugal

    M. I. Veiga, P. E. Ferreira, J. P. Martins, I. Cavaco, V. Ribeiro & J. P. Gil

  4. National Institute of Malariology, Parasitology and Entomology, Hanoi, Vietnam

    T. N. Hai

  5. Department of Economics and Statistics, University of Gothenburg, Göteborg, Sweden

    M. G. Petzold

  6. Nordic School of Public Health, Göteborg, Sweden

    M. G. Petzold

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  1. M. I. Veiga
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Correspondence to M. I. Veiga.

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Veiga, M.I., Asimus, S., Ferreira, P.E. et al. Pharmacogenomics of CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and MDR1 in Vietnam. Eur J Clin Pharmacol 65, 355–363 (2009). https://doi.org/10.1007/s00228-008-0573-8

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