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Genomic Ancestry, CYP2D6, CYP2C9, and CYP2C19 Among Latin Americans.
Fernanda Rodrigues-Soares1,2,3, Eva M Peñas-Lledó1,4, Eduardo Tarazona-Santos1,2,5,6
1RIBEF Ibero-American Network of Pharmacogenetics and Pharmacogenomics, Badajoz, Extremadura, Spain.
Clinical Pharmacology and Therapeutics
|August 4, 2019
Summary
Genetic ancestry shapes the distribution of drug-metabolizing enzyme variants (CYP2D6, CYP2C9, CYP2C19) and predicted phenotypes across Ibero-America. This diversity impacts drug response to medications like warfarin and clopidogrel.
Area of Science:
- Pharmacogenomics
- Population Genetics
- Genetics
Background:
- Cytochrome P450 enzymes (CYP2D6, CYP2C9, CYP2C19) are crucial for drug metabolism.
- Genetic variations in these enzymes lead to diverse predicted phenotypes, influencing drug efficacy and safety.
- Understanding pharmacogene distribution in admixed populations is vital for personalized medicine.
Purpose of the Study:
- To characterize the distribution of CYP2D6, CYP2C9, and CYP2C19 variants and predicted phenotypes in Ibero-American populations.
- To investigate the influence of genetic ancestry on the frequencies of these pharmacogenes.
- To provide insights into the prevalence of clinically relevant phenotypes for specific drugs.
Main Methods:
- Genotyping of CYP2D6, CYP2C9, and CYP2C19 variants in over 6,000 individuals from 33 Ibero-American populations.
- Analysis of genetic ancestry in a subset of 3,387 individuals.
- Prediction of metabolic phenotypes based on identified genotypes.
Main Results:
- Continental ancestries significantly determine the frequencies of key pharmacogenes and their alleles.
- European ancestry is associated with decreased-activity alleles CYP2D6*41, CYP2C9*2, and increased-activity allele CYP2C19*17.
- African ancestry is linked to decreased-activity alleles CYP2D6*17 and CYP2D6*29.
- Rare alleles were present in pre-Columbian Native American populations, indicating autochthonous diversity.
Conclusions:
- Genetic ancestry is a primary driver of pharmacogene variant distribution in Ibero-America.
- Autochthonous diversity within Native American populations has shaped pharmacogene allele frequencies.
- Findings offer insights into drug metabolism variations and potential drug response differences for medications like warfarin and clopidogrel.
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