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Pharmacogenomic variabilities in geo-ancestral subpopulations and their clinical implications: Results of collaborations with Hmong in the United States

Underrepresentation of subpopulations within geo-ancestral groups engaged in research can exacerbate health disparities and impair progress toward personalized medicine. This is particularly important when implementing pharmacogenomics which uses genomic-based sources of variability to guide medicat...

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Autores principales: Sun, Boguang, Wen, Ya-Feng, Culhane-Pera, Kathleen A., Lo, Muaj, Straka, Robert J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845584/
https://www.ncbi.nlm.nih.gov/pubmed/36685861
http://dx.doi.org/10.3389/fgene.2022.1070236
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author Sun, Boguang
Wen, Ya-Feng
Culhane-Pera, Kathleen A.
Lo, Muaj
Straka, Robert J.
author_facet Sun, Boguang
Wen, Ya-Feng
Culhane-Pera, Kathleen A.
Lo, Muaj
Straka, Robert J.
author_sort Sun, Boguang
collection PubMed
description Underrepresentation of subpopulations within geo-ancestral groups engaged in research can exacerbate health disparities and impair progress toward personalized medicine. This is particularly important when implementing pharmacogenomics which uses genomic-based sources of variability to guide medication selection and dosing. This mini-review focuses on pharmacogenomic findings with Hmong in the United States and their potential clinical implications. By actively engaging Hmong community in pharmacogenomic-based research, several clinically relevant differences in allele frequencies were observed within key pharmacogenes such as CYP2C9 and CYP2C19 in Hmong compared to those in either East Asians or Europeans. Additionally, using state-of-the-art genome sequencing approaches, Hmong appear to possess novel genetic variants within CYP2D6, a critical pharmacogene affecting pharmacokinetics of a broad range of medications. The allele frequency differences and novel alleles in Hmong have translational impact and real-world clinical consequences. For example, Hmong patients exhibited a lower warfarin stable dose requirement compared to East Asian patients. This was predicted based on Hmong’s unique genetic and non-genetic factors and confirmed using real-world data from clinical practice settings. By presenting evidence of the genetic uniqueness and its translational impact within subpopulations, such as the Hmong, we hope to inspire greater inclusion of other geo-ancestrally underrepresented subpopulations in pharmacogenomic-based research.
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spelling pubmed-98455842023-01-19 Pharmacogenomic variabilities in geo-ancestral subpopulations and their clinical implications: Results of collaborations with Hmong in the United States Sun, Boguang Wen, Ya-Feng Culhane-Pera, Kathleen A. Lo, Muaj Straka, Robert J. Front Genet Genetics Underrepresentation of subpopulations within geo-ancestral groups engaged in research can exacerbate health disparities and impair progress toward personalized medicine. This is particularly important when implementing pharmacogenomics which uses genomic-based sources of variability to guide medication selection and dosing. This mini-review focuses on pharmacogenomic findings with Hmong in the United States and their potential clinical implications. By actively engaging Hmong community in pharmacogenomic-based research, several clinically relevant differences in allele frequencies were observed within key pharmacogenes such as CYP2C9 and CYP2C19 in Hmong compared to those in either East Asians or Europeans. Additionally, using state-of-the-art genome sequencing approaches, Hmong appear to possess novel genetic variants within CYP2D6, a critical pharmacogene affecting pharmacokinetics of a broad range of medications. The allele frequency differences and novel alleles in Hmong have translational impact and real-world clinical consequences. For example, Hmong patients exhibited a lower warfarin stable dose requirement compared to East Asian patients. This was predicted based on Hmong’s unique genetic and non-genetic factors and confirmed using real-world data from clinical practice settings. By presenting evidence of the genetic uniqueness and its translational impact within subpopulations, such as the Hmong, we hope to inspire greater inclusion of other geo-ancestrally underrepresented subpopulations in pharmacogenomic-based research. Frontiers Media S.A. 2023-01-04 /pmc/articles/PMC9845584/ /pubmed/36685861 http://dx.doi.org/10.3389/fgene.2022.1070236 Text en Copyright © 2023 Sun, Wen, Culhane-Pera, Lo and Straka. 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
Sun, Boguang
Wen, Ya-Feng
Culhane-Pera, Kathleen A.
Lo, Muaj
Straka, Robert J.
Pharmacogenomic variabilities in geo-ancestral subpopulations and their clinical implications: Results of collaborations with Hmong in the United States
title Pharmacogenomic variabilities in geo-ancestral subpopulations and their clinical implications: Results of collaborations with Hmong in the United States
title_full Pharmacogenomic variabilities in geo-ancestral subpopulations and their clinical implications: Results of collaborations with Hmong in the United States
title_fullStr Pharmacogenomic variabilities in geo-ancestral subpopulations and their clinical implications: Results of collaborations with Hmong in the United States
title_full_unstemmed Pharmacogenomic variabilities in geo-ancestral subpopulations and their clinical implications: Results of collaborations with Hmong in the United States
title_short Pharmacogenomic variabilities in geo-ancestral subpopulations and their clinical implications: Results of collaborations with Hmong in the United States
title_sort pharmacogenomic variabilities in geo-ancestral subpopulations and their clinical implications: results of collaborations with hmong in the united states
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845584/
https://www.ncbi.nlm.nih.gov/pubmed/36685861
http://dx.doi.org/10.3389/fgene.2022.1070236
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