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CYP2D6 genotype and dextromethorphan hydroxylation phenotype in an Ecuadorian population

  • Pharmacogenetics
  • Published:
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Abstract

Purpose

Cytochrome P450 2D6 (CYP2D6) genotypes and the dextromethorphan/dextrorphan (DXM/DXT) metabolic ratio (MR), which is a marker of CYP2D6 activity, were studied in 118 unrelated healthy Ecuadorians.

Methods

Genotyping of CYP2D6 was performed by amplification of entire CYP2D6 gene by XL-PCR for CYP2D6*5 and multiplication alleles and by real time-PCR for CYP2D6 *2, *3, *4, *6, *10, *17, *29, *35, *41, and copy number. The plasma levels of DXM and its metabolite DXT were determined on a high-performance liquid chromatography–UV system.

Results

The proportions of non-functional alleles were 0.4, 10.6, 0.8, 2.1, and 0% for CYP2D6*3, *4, *4 × N, *5, and *6, respectively. Genotypically, only one of the subjects (0.9%) was homozygous for two inactive alleles and phenotypically classified as a poor metabolizer (PM). The MRs (mean ± standard deviation) corresponding to “activity scores” of 0, 0.5, 1, 1.5, 2, and 2.5 were 10.57 (n = 1), 1.63 ± 0.35 (n = 2), 1.16 ± 0.74 (n = 29), 1.00 ± 0.47 (n = 8), 1.24 ± 0.82 (n = 76), and 1.30 ± 0.32 (n = 2), respectively.

Conclusions

Our data suggest that only 1% of subjects of this Ecuadorian population were PMs and that none were phenotypically ultrarapid metabolizers, which is in agreement with previous findings in other Amerindian populations.

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Acknowledgments

The technical assistance of Inés López and Beatriz Grillo is gratefully acknowledged. We also thank to Eva M. Peñas-Lledó PhD for her fruitful comments and review. This study was partially funded by AEXCID Cooperación Extremeña of Junta de Extremadura (9IA006) and coordinated in the RIBEF network (Red Iberoamericana de Farmacogenética y Farmacogenómica; www.ribef.com). It was also partly supported by the Institute of Health Carlos III-FIS and European Union (FEDER) Grants PI10/02758, PI10/02010, and CP06/00030 (P. Dorado).

Conflict of interest statement

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. CICAB Clinical Research Centre, Extremadura University Hospital and Medical School, Badajoz, Spain

    Pedro Dorado, Esther Machín & Adrián LLerena

  2. Biomedical Centre, Central University of Ecuador, Quito, Ecuador

    Natalia Heras & Enrique Teran

  3. School of Medicine, Universidad Estatal de Guayaquil, Guayaquil, Ecuador

    Francisco Hernández

  4. Health Science College, Universidad San Francisco de Quito, Quito, Ecuador

    Enrique Teran

  5. SES Servicio Extremeño de Salud, Hospital Universitario Infanta Cristina, University of Extremadura, 06080, Badajoz, Spain

    Adrián LLerena

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  1. Pedro Dorado
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  2. Natalia Heras
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  3. Esther Machín
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  4. Francisco Hernández
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  5. Enrique Teran
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  6. Adrián LLerena
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Corresponding authors

Correspondence to Enrique Teran or Adrián LLerena.

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Dorado, P., Heras, N., Machín, E. et al. CYP2D6 genotype and dextromethorphan hydroxylation phenotype in an Ecuadorian population. Eur J Clin Pharmacol 68, 637–644 (2012). https://doi.org/10.1007/s00228-011-1147-8

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  • DOI: https://doi.org/10.1007/s00228-011-1147-8

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