CYP2D6 gene polymorphisms and predicted phenotypes in eight indigenous groups from northwestern Mexico

Abstract

Aim: Polymorphisms in CYP2D6 impact the interindividual and interethnic variability of drug efficiency; therefore, we determined the CYP2D6 allele distribution in eight Amerindian groups from northwestern Mexico and compared them with the frequencies in Mexican Mestizos. Materials & methods: A total of 508 Amerindians were studied. Genotyping of CYP2D6 5 and multiplication alleles was performed by long-range PCR, while CYP2D62,3,4,6,10,17,29,35,41 and copy number were evaluated by real-time PCR. Results: The most frequent alleles were CYP2D62 (0.05-0.28), CYP2D64 (0.003-0.21) and multiplications (0.043-0.107). CYP2D65,6, * 10 and41 were not observed in the majority of Amerindians, and CYP2D63,17,35 and29 were not detected. The poor metabolizer genotype (4/5) was lower (0.2%) in Amerindians than in Mestizos (5%); conversely, the ultrarapid metabolizer genotype was higher (12.6%) in indigenous groups than in Mestizos (7%). Conclusion: Our data show a lower frequency of CYP2D6 inactive alleles and a higher frequency of duplication/multiplication of CYP2D6 active alleles in indigenous populations that in Mestizos.