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Metabolizer phenotype prediction in different Peruvian ethnic groups through CYP2C9 polymorphisms.

Edward Valencia Ayala1,2, Mylenka Chevarría Arriaga2, Eduardo Barbosa Coelho3

  • 1Facultad de Medicina Humana, Universidad de San Martin de Porres, Centro de Investigación en Infectología e Inmunología-Instituto de Investigación, La Molina, Lima, Peru.

Drug Metabolism and Personalized Therapy
|March 18, 2021
PubMed
Summary

CYP2C9 genetic variations influence drug metabolism phenotypes across Peruvian ethnic groups. This study identified distinct CYP2C9 allele frequencies and metabolizer phenotypes in Andean, Coast, and Amazonian populations, informing personalized medicine strategies.

Keywords:
allelic variantsethnic populationgenotypingmetabolizer phenotype

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Area of Science:

  • Pharmacogenomics
  • Human Genetics
  • Drug Metabolism

Background:

  • The CYP2C9 gene exhibits common alleles (*1, *2, *3) influencing drug metabolism.
  • Genotypes (*1/*1, *2/*2, *3/*3, *1/*2, *1/*3) determine metabolizer phenotypes: extensive (gEM), intermediate (gIM), and poor (gPM).
  • Inter-ethnic variability in drug metabolism necessitates population-specific studies.

Purpose of the Study:

  • To predict CYP2C9 metabolizer phenotypes in diverse Peruvian ethnic groups.
  • To analyze genetic variations in lowland (<2,500m) and highland (>2,500m) Peruvian populations.
  • To understand the association between CYP2C9 alleles and metabolizer phenotypes in different eco-regions of Peru.

Main Methods:

  • TaqMan genotyping assays were employed.
  • A cohort of 174 healthy, unrelated Peruvian individuals was studied.
  • Allelic frequencies and genotype distributions were analyzed across three eco-regions.

Main Results:

  • CYP2C9*1 was most prevalent in the Andean population (96.32%).
  • CYP2C9*2 was most frequent on the Coast (7.45%, p<0.05), and CYP2C9*3 in the Amazonian region (6.25%, p<0.05).
  • Extensive metabolizers (gEM) predominated in the Andean population (94.74%), intermediate metabolizers (gIM) on the Coast (17.02%), and poor metabolizers (gPM) in the Amazonian population (6.25%).

Conclusions:

  • This study provides crucial data on CYP2C9 metabolizer phenotypes in distinct Peruvian ethnic groups.
  • Findings highlight significant inter-ethnic variability in CYP2C9 allele frequencies and associated drug metabolism.
  • Results can guide the development of suitable genetic-dosage strategies for common diseases in Peru's heterogeneous populations.