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Towards Accurate Genotype–Phenotype Correlations in the CYP2D6 Gene

Establishing accurate and large-scale genotype–phenotype correlations and predictions of individual response to pharmacological treatments are two of the holy grails of Personalized Medicine. These tasks are challenging and require an integrated knowledge of the complex processes that regulate gene...

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Autor principal: Pey, Angel L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711719/
https://www.ncbi.nlm.nih.gov/pubmed/33049937
http://dx.doi.org/10.3390/jpm10040158
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author Pey, Angel L.
author_facet Pey, Angel L.
author_sort Pey, Angel L.
collection PubMed
description Establishing accurate and large-scale genotype–phenotype correlations and predictions of individual response to pharmacological treatments are two of the holy grails of Personalized Medicine. These tasks are challenging and require an integrated knowledge of the complex processes that regulate gene expression and, ultimately, protein functionality in vivo, the effects of mutations/polymorphisms and the different sources of interindividual phenotypic variability. A remarkable example of our advances in these challenging tasks is the highly polymorphic CYP2D6 gene, which encodes a cytochrome P450 enzyme involved in the metabolization of many of the most marketed drugs (including SARS-Cov-2 therapies such as hydroxychloroquine). Since the introduction of simple activity scores (AS) over 10 years ago, its ability to establish genotype–phenotype correlations on the drug metabolizing capacity of this enzyme in human population has provided lessons that will help to improve this type of score for this, and likely many other human genes and proteins. Multidisciplinary research emerges as the best approach to incorporate additional concepts to refine and improve such functional/activity scores for the CYP2D6 gene, as well as for many other human genes associated with simple and complex genetic diseases.
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spelling pubmed-77117192020-12-04 Towards Accurate Genotype–Phenotype Correlations in the CYP2D6 Gene Pey, Angel L. J Pers Med Editorial Establishing accurate and large-scale genotype–phenotype correlations and predictions of individual response to pharmacological treatments are two of the holy grails of Personalized Medicine. These tasks are challenging and require an integrated knowledge of the complex processes that regulate gene expression and, ultimately, protein functionality in vivo, the effects of mutations/polymorphisms and the different sources of interindividual phenotypic variability. A remarkable example of our advances in these challenging tasks is the highly polymorphic CYP2D6 gene, which encodes a cytochrome P450 enzyme involved in the metabolization of many of the most marketed drugs (including SARS-Cov-2 therapies such as hydroxychloroquine). Since the introduction of simple activity scores (AS) over 10 years ago, its ability to establish genotype–phenotype correlations on the drug metabolizing capacity of this enzyme in human population has provided lessons that will help to improve this type of score for this, and likely many other human genes and proteins. Multidisciplinary research emerges as the best approach to incorporate additional concepts to refine and improve such functional/activity scores for the CYP2D6 gene, as well as for many other human genes associated with simple and complex genetic diseases. MDPI 2020-10-08 /pmc/articles/PMC7711719/ /pubmed/33049937 http://dx.doi.org/10.3390/jpm10040158 Text en © 2020 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Editorial
Pey, Angel L.
Towards Accurate Genotype–Phenotype Correlations in the CYP2D6 Gene
title Towards Accurate Genotype–Phenotype Correlations in the CYP2D6 Gene
title_full Towards Accurate Genotype–Phenotype Correlations in the CYP2D6 Gene
title_fullStr Towards Accurate Genotype–Phenotype Correlations in the CYP2D6 Gene
title_full_unstemmed Towards Accurate Genotype–Phenotype Correlations in the CYP2D6 Gene
title_short Towards Accurate Genotype–Phenotype Correlations in the CYP2D6 Gene
title_sort towards accurate genotype–phenotype correlations in the cyp2d6 gene
topic Editorial
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711719/
https://www.ncbi.nlm.nih.gov/pubmed/33049937
http://dx.doi.org/10.3390/jpm10040158
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