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Why We Need to Take a Closer Look at Genetic Contributions to CYP3A Activity

Cytochrome P450 3A (CYP3A) subfamily enzymes are involved in the metabolism of 40% of drugs in clinical use. Twin studies have indicated that 66% of the variability in CYP3A4 activity is hereditary. Yet, the complexity of the CYP3A locus and the lack of distinct drug metabolizer phenotypes has limit...

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Autores principales: Zhai, Qinglian, van der Lee, Maaike, van Gelder, Teun, Swen, Jesse J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243486/
https://www.ncbi.nlm.nih.gov/pubmed/35784699
http://dx.doi.org/10.3389/fphar.2022.912618
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author Zhai, Qinglian
van der Lee, Maaike
van Gelder, Teun
Swen, Jesse J.
author_facet Zhai, Qinglian
van der Lee, Maaike
van Gelder, Teun
Swen, Jesse J.
author_sort Zhai, Qinglian
collection PubMed
description Cytochrome P450 3A (CYP3A) subfamily enzymes are involved in the metabolism of 40% of drugs in clinical use. Twin studies have indicated that 66% of the variability in CYP3A4 activity is hereditary. Yet, the complexity of the CYP3A locus and the lack of distinct drug metabolizer phenotypes has limited the identification and clinical application of CYP3A genetic variants compared to other Cytochrome P450 enzymes. In recent years evidence has emerged indicating that a substantial part of the missing heritability is caused by low frequency genetic variation. In this review, we outline the current pharmacogenomics knowledge of CYP3A activity and discuss potential future directions to improve our genetic knowledge and ability to explain CYP3A variability.
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spelling pubmed-92434862022-07-01 Why We Need to Take a Closer Look at Genetic Contributions to CYP3A Activity Zhai, Qinglian van der Lee, Maaike van Gelder, Teun Swen, Jesse J. Front Pharmacol Pharmacology Cytochrome P450 3A (CYP3A) subfamily enzymes are involved in the metabolism of 40% of drugs in clinical use. Twin studies have indicated that 66% of the variability in CYP3A4 activity is hereditary. Yet, the complexity of the CYP3A locus and the lack of distinct drug metabolizer phenotypes has limited the identification and clinical application of CYP3A genetic variants compared to other Cytochrome P450 enzymes. In recent years evidence has emerged indicating that a substantial part of the missing heritability is caused by low frequency genetic variation. In this review, we outline the current pharmacogenomics knowledge of CYP3A activity and discuss potential future directions to improve our genetic knowledge and ability to explain CYP3A variability. Frontiers Media S.A. 2022-06-16 /pmc/articles/PMC9243486/ /pubmed/35784699 http://dx.doi.org/10.3389/fphar.2022.912618 Text en Copyright © 2022 Zhai, van der Lee, van Gelder and Swen. 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
Zhai, Qinglian
van der Lee, Maaike
van Gelder, Teun
Swen, Jesse J.
Why We Need to Take a Closer Look at Genetic Contributions to CYP3A Activity
title Why We Need to Take a Closer Look at Genetic Contributions to CYP3A Activity
title_full Why We Need to Take a Closer Look at Genetic Contributions to CYP3A Activity
title_fullStr Why We Need to Take a Closer Look at Genetic Contributions to CYP3A Activity
title_full_unstemmed Why We Need to Take a Closer Look at Genetic Contributions to CYP3A Activity
title_short Why We Need to Take a Closer Look at Genetic Contributions to CYP3A Activity
title_sort why we need to take a closer look at genetic contributions to cyp3a activity
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243486/
https://www.ncbi.nlm.nih.gov/pubmed/35784699
http://dx.doi.org/10.3389/fphar.2022.912618
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