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

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 CYP2D65 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). CYP2D6*5, *6, * 10 and 41 were not observed in the majority of Amerindians, and CYP2D63, *17, *35 and *29 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. Original submitted 14 August 2013; Revision submitted 7 October 2013.