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Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock

BACKGROUND: Pharmacogenetics could represent a further resource to understand the interindividual heterogeneity of response of the host to sepsis and to provide a personalized approach to the critical care patient. METHODS: Secondary analysis of data from the prospective observational study NCT02750...

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Autores principales: Scorcella, C., Domizi, R., Amoroso, S., Carsetti, A., Casarotta, E., Castaldo, P., D’angelo, C., Damiani, E., Gasparri, F., Donati, A., Adrario, E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933278/
https://www.ncbi.nlm.nih.gov/pubmed/36797680
http://dx.doi.org/10.1186/s12871-023-02018-y
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author Scorcella, C.
Domizi, R.
Amoroso, S.
Carsetti, A.
Casarotta, E.
Castaldo, P.
D’angelo, C.
Damiani, E.
Gasparri, F.
Donati, A.
Adrario, E.
author_facet Scorcella, C.
Domizi, R.
Amoroso, S.
Carsetti, A.
Casarotta, E.
Castaldo, P.
D’angelo, C.
Damiani, E.
Gasparri, F.
Donati, A.
Adrario, E.
author_sort Scorcella, C.
collection PubMed
description BACKGROUND: Pharmacogenetics could represent a further resource to understand the interindividual heterogeneity of response of the host to sepsis and to provide a personalized approach to the critical care patient. METHODS: Secondary analysis of data from the prospective observational study NCT02750163, in 50 adult septic and septic shock patients treated with Acetaminophen (ACT) for pyrexia. We investigated the presence of two polymorphisms, located respectively in the genes UGT1A1 and CYP3A5, that encode for proteins related to the hepatic metabolism of ACT. The main dependent variables explored were plasmatic concentration of ACT, body temperature and hepatic parameters. RESULTS: 8% of the patients carried CYP3A5 rs776746 A/G genotypes and showed significantly higher plasma levels of ACT than GG wild type patients, and than patients with UGT1A1 rs8330 C/G genotypes. CONCLUSIONS: Identifying specific genotypes of response to ACT may be helpful to guide a more personalized titration of therapy in sepsis and septic shock. CYP3A5 might be a good biomarker for ACT metabolism; however further studies are needed to confirm this result. TRIAL REGISTRATION: NCT02750163.
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spelling pubmed-99332782023-02-17 Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock Scorcella, C. Domizi, R. Amoroso, S. Carsetti, A. Casarotta, E. Castaldo, P. D’angelo, C. Damiani, E. Gasparri, F. Donati, A. Adrario, E. BMC Anesthesiol Research BACKGROUND: Pharmacogenetics could represent a further resource to understand the interindividual heterogeneity of response of the host to sepsis and to provide a personalized approach to the critical care patient. METHODS: Secondary analysis of data from the prospective observational study NCT02750163, in 50 adult septic and septic shock patients treated with Acetaminophen (ACT) for pyrexia. We investigated the presence of two polymorphisms, located respectively in the genes UGT1A1 and CYP3A5, that encode for proteins related to the hepatic metabolism of ACT. The main dependent variables explored were plasmatic concentration of ACT, body temperature and hepatic parameters. RESULTS: 8% of the patients carried CYP3A5 rs776746 A/G genotypes and showed significantly higher plasma levels of ACT than GG wild type patients, and than patients with UGT1A1 rs8330 C/G genotypes. CONCLUSIONS: Identifying specific genotypes of response to ACT may be helpful to guide a more personalized titration of therapy in sepsis and septic shock. CYP3A5 might be a good biomarker for ACT metabolism; however further studies are needed to confirm this result. TRIAL REGISTRATION: NCT02750163. BioMed Central 2023-02-16 /pmc/articles/PMC9933278/ /pubmed/36797680 http://dx.doi.org/10.1186/s12871-023-02018-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Scorcella, C.
Domizi, R.
Amoroso, S.
Carsetti, A.
Casarotta, E.
Castaldo, P.
D’angelo, C.
Damiani, E.
Gasparri, F.
Donati, A.
Adrario, E.
Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock
title Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock
title_full Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock
title_fullStr Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock
title_full_unstemmed Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock
title_short Pharmacogenetics in critical care: association between CYP3A5 rs776746 A/G genotype and acetaminophen response in sepsis and septic shock
title_sort pharmacogenetics in critical care: association between cyp3a5 rs776746 a/g genotype and acetaminophen response in sepsis and septic shock
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9933278/
https://www.ncbi.nlm.nih.gov/pubmed/36797680
http://dx.doi.org/10.1186/s12871-023-02018-y
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