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Clinically important alterations in pharmacogene expression in histologically severe nonalcoholic fatty liver disease
Polypharmacy is common in patients with nonalcoholic fatty liver disease (NAFLD) and previous reports suggest that NAFLD is associated with altered drug disposition. This study aims to determine if patients with NAFLD are at risk for altered drug response by characterizing changes in hepatic mRNA ex...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10020163/ https://www.ncbi.nlm.nih.gov/pubmed/36927865 http://dx.doi.org/10.1038/s41467-023-37209-1 |
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author | Powell, Nicholas R. Liang, Tiebing Ipe, Joseph Cao, Sha Skaar, Todd C. Desta, Zeruesenay Qian, Hui-Rong Ebert, Philip J. Chen, Yu Thomas, Melissa K. Chalasani, Naga |
author_facet | Powell, Nicholas R. Liang, Tiebing Ipe, Joseph Cao, Sha Skaar, Todd C. Desta, Zeruesenay Qian, Hui-Rong Ebert, Philip J. Chen, Yu Thomas, Melissa K. Chalasani, Naga |
author_sort | Powell, Nicholas R. |
collection | PubMed |
description | Polypharmacy is common in patients with nonalcoholic fatty liver disease (NAFLD) and previous reports suggest that NAFLD is associated with altered drug disposition. This study aims to determine if patients with NAFLD are at risk for altered drug response by characterizing changes in hepatic mRNA expression of genes mediating drug disposition (pharmacogenes) across the histological NAFLD severity spectrum. We utilize RNA-seq for 93 liver biopsies with histologically staged NAFLD Activity Score (NAS), fibrosis stage, and steatohepatitis (NASH). We identify 37 significant pharmacogene-NAFLD severity associations including CYP2C19 downregulation. We chose to validate CYP2C19 due to its actionability in drug prescribing. Meta-analysis of 16 independent studies demonstrate that CYP2C19 is significantly downregulated to 46% in NASH, to 58% in high NAS, and to 43% in severe fibrosis. Our data demonstrate the downregulation of CYP2C19 in NAFLD which supports developing personalized medicine approaches for drugs sensitive to metabolism by the CYP2C19 enzyme. |
format | Online Article Text |
id | pubmed-10020163 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-100201632023-03-18 Clinically important alterations in pharmacogene expression in histologically severe nonalcoholic fatty liver disease Powell, Nicholas R. Liang, Tiebing Ipe, Joseph Cao, Sha Skaar, Todd C. Desta, Zeruesenay Qian, Hui-Rong Ebert, Philip J. Chen, Yu Thomas, Melissa K. Chalasani, Naga Nat Commun Article Polypharmacy is common in patients with nonalcoholic fatty liver disease (NAFLD) and previous reports suggest that NAFLD is associated with altered drug disposition. This study aims to determine if patients with NAFLD are at risk for altered drug response by characterizing changes in hepatic mRNA expression of genes mediating drug disposition (pharmacogenes) across the histological NAFLD severity spectrum. We utilize RNA-seq for 93 liver biopsies with histologically staged NAFLD Activity Score (NAS), fibrosis stage, and steatohepatitis (NASH). We identify 37 significant pharmacogene-NAFLD severity associations including CYP2C19 downregulation. We chose to validate CYP2C19 due to its actionability in drug prescribing. Meta-analysis of 16 independent studies demonstrate that CYP2C19 is significantly downregulated to 46% in NASH, to 58% in high NAS, and to 43% in severe fibrosis. Our data demonstrate the downregulation of CYP2C19 in NAFLD which supports developing personalized medicine approaches for drugs sensitive to metabolism by the CYP2C19 enzyme. Nature Publishing Group UK 2023-03-17 /pmc/articles/PMC10020163/ /pubmed/36927865 http://dx.doi.org/10.1038/s41467-023-37209-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Powell, Nicholas R. Liang, Tiebing Ipe, Joseph Cao, Sha Skaar, Todd C. Desta, Zeruesenay Qian, Hui-Rong Ebert, Philip J. Chen, Yu Thomas, Melissa K. Chalasani, Naga Clinically important alterations in pharmacogene expression in histologically severe nonalcoholic fatty liver disease |
title | Clinically important alterations in pharmacogene expression in histologically severe nonalcoholic fatty liver disease |
title_full | Clinically important alterations in pharmacogene expression in histologically severe nonalcoholic fatty liver disease |
title_fullStr | Clinically important alterations in pharmacogene expression in histologically severe nonalcoholic fatty liver disease |
title_full_unstemmed | Clinically important alterations in pharmacogene expression in histologically severe nonalcoholic fatty liver disease |
title_short | Clinically important alterations in pharmacogene expression in histologically severe nonalcoholic fatty liver disease |
title_sort | clinically important alterations in pharmacogene expression in histologically severe nonalcoholic fatty liver disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10020163/ https://www.ncbi.nlm.nih.gov/pubmed/36927865 http://dx.doi.org/10.1038/s41467-023-37209-1 |
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