CYP2D6 gene variants in urban/admixed and Amerindian populations of Venezuela: Pharmacogenetics and anthropological implications

Background: Differences in genes encoding enzymes involved in the biotransformation of a large number of compounds, such as CYP2D6, are related to inter-individual and inter-ethnic variability in the metabolism of many drugs, which have also been linked to susceptibility to cancer and other health outcomes. Therefore, populations are likely to benefit from inclusion in pharmacogenetic research studies. Aim: To determine the frequency of functionally important allele variants of CYP2D6 gene in a sample of an Urban/admixed and five Amerindian Venezuelan populations. Subjects and methods: DNA of 328 unrelated volunteers was analysed for the presence of CYP2D6 *2, *3, *4, *5, *6 and *10 variants. Results: The frequency in the Urban/admixed population for *2, *3, *4, *5, *6 and *10 alleles was 37.9%, 0%, 13.4%, 2.0%, 1.2% and 4.0%, respectively. In the Bari population, the prevalence of *4 allele associated with decreased enzyme activity was observed in 42.5%, whereas the poor metabolizer genotype *4/*4 was found in 25%. In the Panare, Pemon, Warao and Wayuu populations the *4 allele was found in 5.4%, 2.5%, 1.7% and 4.2%, respectively. The *10 allele frequency found in Amerindians (0.0-6.3%) was lower than reported for Asians. Conclusion: The results are consistent with the known genetic admixture origin of most Venezuela populations. Nevertheless, the observed significant differences among Amerindians highlight the need for pharmacogenetic studies taking into account biogeographical and anthropological considerations.