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

Pharmacogenomics. 2014 Feb;15(3):339-48. doi: 10.2217/pgs.13.203.

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 CYP2D6*2, *3, *4, *6, *10, *17, *29, *35, *41 and copy number were evaluated by real-time PCR.

Results: The most frequent alleles were CYP2D6*2 (0.05-0.28), CYP2D6*4 (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 CYP2D6*3, *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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cytochrome P-450 CYP2D6 / genetics*
  • Cytochrome P-450 CYP2D6 / metabolism
  • Gene Frequency*
  • Genotype
  • Humans
  • Inactivation, Metabolic / genetics*
  • Indians, North American / genetics*
  • Mexico
  • Phenotype

Substances

  • Cytochrome P-450 CYP2D6