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CYP2D6 genotype and dextromethorphan hydroxylation phenotype in an Ecuadorian population

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. © Springer-Verlag 2011.