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Distribution of a novel CYP2C haplotype in Native American populations

The CYP2C19 gene, located in the CYP2C cluster, encodes the major drug metabolism enzyme CYP2C19. This gene is highly polymorphic and no-function (CYP2C19*2 and CYP2C19*3), reduced function (CYP2C19*9) and increased function (CYP2C19*17) star alleles (haplotypes) are commonly used to predict CYP2C19...

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Autores principales: Fernandes, Vanessa Câmara, Pretti, Marco Antônio M., Tsuneto, Luiza Tamie, Petzl-Erler, Maria Luiza, Suarez-Kurtz, Guilherme
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10071019/
https://www.ncbi.nlm.nih.gov/pubmed/37025454
http://dx.doi.org/10.3389/fgene.2023.1114742
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author Fernandes, Vanessa Câmara
Pretti, Marco Antônio M.
Tsuneto, Luiza Tamie
Petzl-Erler, Maria Luiza
Suarez-Kurtz, Guilherme
author_facet Fernandes, Vanessa Câmara
Pretti, Marco Antônio M.
Tsuneto, Luiza Tamie
Petzl-Erler, Maria Luiza
Suarez-Kurtz, Guilherme
author_sort Fernandes, Vanessa Câmara
collection PubMed
description The CYP2C19 gene, located in the CYP2C cluster, encodes the major drug metabolism enzyme CYP2C19. This gene is highly polymorphic and no-function (CYP2C19*2 and CYP2C19*3), reduced function (CYP2C19*9) and increased function (CYP2C19*17) star alleles (haplotypes) are commonly used to predict CYP2C19 metabolic phenotypes. CYP2C19*17 and the genotype-predicted rapid (RM) and ultrarapid (UM) CYP2C19 metabolic phenotypes are absent or rare in several Native American populations. However, discordance between genotype-predicted and pharmacokinetically determined CYP2C19 phenotypes in Native American cohorts have been reported. Recently, a haplotype defined by rs2860840T and rs11188059G alleles in the CYP2C cluster has been shown to encode increased rate of metabolism of the CYP2C19 substrate escitalopram, to a similar extent as CYP2C19*17. We investigated the distribution of the CYP2C:TG haplotype and explored its potential impact on CYP2C19 metabolic activity in Native American populations. The study cohorts included individuals from the One Thousand Genomes Project AMR superpopulation (1 KG_AMR), the Human Genome Diversity Project (HGDP), and from indigenous populations living in Brazil (Kaingang and Guarani). The frequency range of the CYP2C:TG haplotype in the study cohorts, 0.469 to 0.598, is considerably higher than in all 1 KG superpopulations (range: 0.014—to 0.340). We suggest that the high frequency of the CYP2C:TG haplotype might contribute to the reported discordance between CYP2C19-predicted and pharmacokinetically verified CYP2C19 metabolic phenotypes in Native American cohorts. However, functional studies involving genotypic correlations with pharmacokinetic parameters are warranted to ascertain the importance of the CYP2C:TG haplotype.
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spelling pubmed-100710192023-04-05 Distribution of a novel CYP2C haplotype in Native American populations Fernandes, Vanessa Câmara Pretti, Marco Antônio M. Tsuneto, Luiza Tamie Petzl-Erler, Maria Luiza Suarez-Kurtz, Guilherme Front Genet Genetics The CYP2C19 gene, located in the CYP2C cluster, encodes the major drug metabolism enzyme CYP2C19. This gene is highly polymorphic and no-function (CYP2C19*2 and CYP2C19*3), reduced function (CYP2C19*9) and increased function (CYP2C19*17) star alleles (haplotypes) are commonly used to predict CYP2C19 metabolic phenotypes. CYP2C19*17 and the genotype-predicted rapid (RM) and ultrarapid (UM) CYP2C19 metabolic phenotypes are absent or rare in several Native American populations. However, discordance between genotype-predicted and pharmacokinetically determined CYP2C19 phenotypes in Native American cohorts have been reported. Recently, a haplotype defined by rs2860840T and rs11188059G alleles in the CYP2C cluster has been shown to encode increased rate of metabolism of the CYP2C19 substrate escitalopram, to a similar extent as CYP2C19*17. We investigated the distribution of the CYP2C:TG haplotype and explored its potential impact on CYP2C19 metabolic activity in Native American populations. The study cohorts included individuals from the One Thousand Genomes Project AMR superpopulation (1 KG_AMR), the Human Genome Diversity Project (HGDP), and from indigenous populations living in Brazil (Kaingang and Guarani). The frequency range of the CYP2C:TG haplotype in the study cohorts, 0.469 to 0.598, is considerably higher than in all 1 KG superpopulations (range: 0.014—to 0.340). We suggest that the high frequency of the CYP2C:TG haplotype might contribute to the reported discordance between CYP2C19-predicted and pharmacokinetically verified CYP2C19 metabolic phenotypes in Native American cohorts. However, functional studies involving genotypic correlations with pharmacokinetic parameters are warranted to ascertain the importance of the CYP2C:TG haplotype. Frontiers Media S.A. 2023-03-21 /pmc/articles/PMC10071019/ /pubmed/37025454 http://dx.doi.org/10.3389/fgene.2023.1114742 Text en Copyright © 2023 Fernandes, Pretti, Tsuneto, Petzl-Erler and Suarez-Kurtz. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Fernandes, Vanessa Câmara
Pretti, Marco Antônio M.
Tsuneto, Luiza Tamie
Petzl-Erler, Maria Luiza
Suarez-Kurtz, Guilherme
Distribution of a novel CYP2C haplotype in Native American populations
title Distribution of a novel CYP2C haplotype in Native American populations
title_full Distribution of a novel CYP2C haplotype in Native American populations
title_fullStr Distribution of a novel CYP2C haplotype in Native American populations
title_full_unstemmed Distribution of a novel CYP2C haplotype in Native American populations
title_short Distribution of a novel CYP2C haplotype in Native American populations
title_sort distribution of a novel cyp2c haplotype in native american populations
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10071019/
https://www.ncbi.nlm.nih.gov/pubmed/37025454
http://dx.doi.org/10.3389/fgene.2023.1114742
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