CYP2D6 genotype and dextromethorphan hydroxylation phenotype in an Ecuadorian population

Eur J Clin Pharmacol. 2012 May;68(5):637-44. doi: 10.1007/s00228-011-1147-8. Epub 2011 Nov 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Antitussive Agents / blood
  • Antitussive Agents / pharmacokinetics*
  • Biotransformation
  • Cytochrome P-450 CYP2D6 / genetics*
  • Cytochrome P-450 CYP2D6 / metabolism
  • Dextromethorphan / blood
  • Dextromethorphan / pharmacokinetics*
  • Dextrorphan / blood
  • Ecuador
  • Female
  • Gene Dosage
  • Gene Frequency
  • Genetic Association Studies
  • Humans
  • Hydroxylation
  • Male
  • Polymorphism, Genetic*
  • Young Adult

Substances

  • Antitussive Agents
  • Dextrorphan
  • Dextromethorphan
  • Cytochrome P-450 CYP2D6