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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.912618/full |
| _version_ | 1818231647019991040 |
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| author | Qinglian Zhai Maaike van der Lee Teun van Gelder Jesse J. Swen |
| author_facet | Qinglian Zhai Maaike van der Lee Teun van Gelder Jesse J. Swen |
| author_sort | Qinglian Zhai |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T10:53:43Z |
| format | Article |
| id | doaj.art-095cfae0737147a89d788acdd098a335 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-12T10:53:43Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-095cfae0737147a89d788acdd098a3352022-12-22T00:26:43ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-06-011310.3389/fphar.2022.912618912618Why We Need to Take a Closer Look at Genetic Contributions to CYP3A ActivityQinglian ZhaiMaaike van der LeeTeun van GelderJesse J. SwenCytochrome 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.912618/fullCYP3A locusCYP3A4CYP3A5genetic variantsenzyme activitymissing heritability |
| spellingShingle | Qinglian Zhai Maaike van der Lee Teun van Gelder Jesse J. Swen Why We Need to Take a Closer Look at Genetic Contributions to CYP3A Activity Frontiers in Pharmacology CYP3A locus CYP3A4 CYP3A5 genetic variants enzyme activity missing heritability |
| 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 | CYP3A locus CYP3A4 CYP3A5 genetic variants enzyme activity missing heritability |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.912618/full |
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