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Single Nucleotide Variants as Proxies for HLA-A*31:01 in Native American Populations

Carbamazepine triggers dermatologic hypersensitivity reactions, associated with specific human leukocyte antigens (HLAs), especially HLA-B*15:02 and HLA-A*31:01. Previous efforts to identify single nucleotide variants (SNVs) with high predictive value as HLA proxies, revealed that rs1061235 and rs17...

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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. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046591/
https://www.ncbi.nlm.nih.gov/pubmed/35496269
http://dx.doi.org/10.3389/fphar.2022.849136
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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 Carbamazepine triggers dermatologic hypersensitivity reactions, associated with specific human leukocyte antigens (HLAs), especially HLA-B*15:02 and HLA-A*31:01. Previous efforts to identify single nucleotide variants (SNVs) with high predictive value as HLA proxies, revealed that rs1061235 and rs17179220 fulfill these requirements for HLA-A*31:01 in some but not all populations. Herein we explored the predictive performance of rs1061235 and rs17179220 as HLA-A*31:01 tags in populations of Native American ancestry, which are largely underrepresented in pharmacogenomic studies. The study cohorts comprised the overall Admixed American superpopulation of the 1000 Genomes Project (1 KG_AMR), a subcohort of individuals with predominant Native American ancestry (1 KG_NAT), the Native American population of the Human Genome Diversity Project (HGDP), plus Kaingang (KRC) and Guarani (GRC and GKW) adults from indigenous reservation areas in Brazil. The diversity of cohorts is reflected in the range of frequencies of HLA-A*31:01 (0.02–0.65), rs1061235 (0.03–0.13) and rs17179220 (0.12–0.66), as well as in the predictive performance of these SNVs as HLA-A*31:01 proxies. NPV (negative predictive value), the metric of primary interest for pharmacogenetic-informed carbamazepine prescription was maximal (NPV = 1.0) for both SNVs in 1 KG_AMR and 1 KG_NAT, for rs17179220, but not rs1061235 (NPV = 0.91) in HGDP, and for rs17179220 in GWK, but not GRC (NPV = 0.88) or KRC (NPV = 0.80). Collectively, the data support the notion that rs1061235 and rs17179220 are not optimal proxies for HLA-A*31:01 across populations of Native American ancestry.
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spelling pubmed-90465912022-04-29 Single Nucleotide Variants as Proxies for HLA-A*31:01 in Native American Populations Fernandes, Vanessa Câmara Pretti, Marco Antônio M. Tsuneto, Luiza Tamie Petzl-Erler, Maria Luiza Suarez-Kurtz, Guilherme Front Pharmacol Pharmacology Carbamazepine triggers dermatologic hypersensitivity reactions, associated with specific human leukocyte antigens (HLAs), especially HLA-B*15:02 and HLA-A*31:01. Previous efforts to identify single nucleotide variants (SNVs) with high predictive value as HLA proxies, revealed that rs1061235 and rs17179220 fulfill these requirements for HLA-A*31:01 in some but not all populations. Herein we explored the predictive performance of rs1061235 and rs17179220 as HLA-A*31:01 tags in populations of Native American ancestry, which are largely underrepresented in pharmacogenomic studies. The study cohorts comprised the overall Admixed American superpopulation of the 1000 Genomes Project (1 KG_AMR), a subcohort of individuals with predominant Native American ancestry (1 KG_NAT), the Native American population of the Human Genome Diversity Project (HGDP), plus Kaingang (KRC) and Guarani (GRC and GKW) adults from indigenous reservation areas in Brazil. The diversity of cohorts is reflected in the range of frequencies of HLA-A*31:01 (0.02–0.65), rs1061235 (0.03–0.13) and rs17179220 (0.12–0.66), as well as in the predictive performance of these SNVs as HLA-A*31:01 proxies. NPV (negative predictive value), the metric of primary interest for pharmacogenetic-informed carbamazepine prescription was maximal (NPV = 1.0) for both SNVs in 1 KG_AMR and 1 KG_NAT, for rs17179220, but not rs1061235 (NPV = 0.91) in HGDP, and for rs17179220 in GWK, but not GRC (NPV = 0.88) or KRC (NPV = 0.80). Collectively, the data support the notion that rs1061235 and rs17179220 are not optimal proxies for HLA-A*31:01 across populations of Native American ancestry. Frontiers Media S.A. 2022-04-14 /pmc/articles/PMC9046591/ /pubmed/35496269 http://dx.doi.org/10.3389/fphar.2022.849136 Text en Copyright © 2022 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 Pharmacology
Fernandes, Vanessa Câmara
Pretti, Marco Antônio M.
Tsuneto, Luiza Tamie
Petzl-Erler, Maria Luiza
Suarez-Kurtz, Guilherme
Single Nucleotide Variants as Proxies for HLA-A*31:01 in Native American Populations
title Single Nucleotide Variants as Proxies for HLA-A*31:01 in Native American Populations
title_full Single Nucleotide Variants as Proxies for HLA-A*31:01 in Native American Populations
title_fullStr Single Nucleotide Variants as Proxies for HLA-A*31:01 in Native American Populations
title_full_unstemmed Single Nucleotide Variants as Proxies for HLA-A*31:01 in Native American Populations
title_short Single Nucleotide Variants as Proxies for HLA-A*31:01 in Native American Populations
title_sort single nucleotide variants as proxies for hla-a*31:01 in native american populations
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046591/
https://www.ncbi.nlm.nih.gov/pubmed/35496269
http://dx.doi.org/10.3389/fphar.2022.849136
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