Future Trends in the Pharmacogenomics of Brain Disorders and Dementia: Influence of APOE and CYP2D6 Variants

About 80% of functional genes in the human genome are expressed in the brain and over 1,200 different genes have been associated with the pathogenesis of CNS disorders and dementia. Pharmacogenetic studies of psychotropic drug response have focused on determining the relationship between variations...

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Main Authors:	Cacabelos, Ramón, Fernández-Novoa, Lucía, Martínez-Bouza, Rocío, McKay, Adam, Carril, Juan C., Lombardi, Valter, Corzo, Lola, Carrera, Iván, Tellado, Iván, Nebril, Laura, Alcaraz, Margarita, Rodríguez, Susana, Casas, Ángela, Couceiro, Verónica, Álvarez, Antón
Format:	Online
Language:	English
Published:	MDPI 2010
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034082/

id	pubmed-4034082
recordtype	oai_dc
spelling	pubmed-40340822014-05-27 Future Trends in the Pharmacogenomics of Brain Disorders and Dementia: Influence of APOE and CYP2D6 Variants Cacabelos, Ramón Fernández-Novoa, Lucía Martínez-Bouza, Rocío McKay, Adam Carril, Juan C. Lombardi, Valter Corzo, Lola Carrera, Iván Tellado, Iván Nebril, Laura Alcaraz, Margarita Rodríguez, Susana Casas, Ángela Couceiro, Verónica Álvarez, Antón Review About 80% of functional genes in the human genome are expressed in the brain and over 1,200 different genes have been associated with the pathogenesis of CNS disorders and dementia. Pharmacogenetic studies of psychotropic drug response have focused on determining the relationship between variations in specific candidate genes and the positive and adverse effects of drug treatment. Approximately, 18% of neuroleptics are substrates of CYP1A2 enzymes, 40% of CYP2D6, and 23% of CYP3A4; 24% of antidepressants are substrates of CYP1A2 enzymes, 5% of CYP2B6, 38% of CYP2C19, 85% of CYP2D6, and 38% of CYP3A4; 7% of benzodiazepines are substrates of CYP2C19 enzymes, 20% of CYP2D6, and 95% of CYP3A4. 10-20% of Western populations are defective in genes of the CYP superfamily; and the pharmacogenomic response of psychotropic drugs also depends on genetic variants associated with dementia. Prospective studies with anti-dementia drugs or with multifactorial strategies have revealed that the therapeutic response to conventional drugs in Alzheimer’s disease is genotype-specific. The disease-modifying effects (cognitive performance, biomarker modification) of therapeutic intervention are APOE-dependent, with APOE-4 carriers acting as the worst responders (APOE-3/3 > APOE-3/4 > APOE-4/4). APOE-CYP2D6 interactions also influence the therapeutic outcome in patients with dementia. MDPI 2010-09-29 /pmc/articles/PMC4034082/ http://dx.doi.org/10.3390/ph3103040 Text en © 2010 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Cacabelos, Ramón Fernández-Novoa, Lucía Martínez-Bouza, Rocío McKay, Adam Carril, Juan C. Lombardi, Valter Corzo, Lola Carrera, Iván Tellado, Iván Nebril, Laura Alcaraz, Margarita Rodríguez, Susana Casas, Ángela Couceiro, Verónica Álvarez, Antón
spellingShingle	Cacabelos, Ramón Fernández-Novoa, Lucía Martínez-Bouza, Rocío McKay, Adam Carril, Juan C. Lombardi, Valter Corzo, Lola Carrera, Iván Tellado, Iván Nebril, Laura Alcaraz, Margarita Rodríguez, Susana Casas, Ángela Couceiro, Verónica Álvarez, Antón Future Trends in the Pharmacogenomics of Brain Disorders and Dementia: Influence of APOE and CYP2D6 Variants
author_facet	Cacabelos, Ramón Fernández-Novoa, Lucía Martínez-Bouza, Rocío McKay, Adam Carril, Juan C. Lombardi, Valter Corzo, Lola Carrera, Iván Tellado, Iván Nebril, Laura Alcaraz, Margarita Rodríguez, Susana Casas, Ángela Couceiro, Verónica Álvarez, Antón
author_sort	Cacabelos, Ramón
title	Future Trends in the Pharmacogenomics of Brain Disorders and Dementia: Influence of APOE and CYP2D6 Variants
title_short	Future Trends in the Pharmacogenomics of Brain Disorders and Dementia: Influence of APOE and CYP2D6 Variants
title_full	Future Trends in the Pharmacogenomics of Brain Disorders and Dementia: Influence of APOE and CYP2D6 Variants
title_fullStr	Future Trends in the Pharmacogenomics of Brain Disorders and Dementia: Influence of APOE and CYP2D6 Variants
title_full_unstemmed	Future Trends in the Pharmacogenomics of Brain Disorders and Dementia: Influence of APOE and CYP2D6 Variants
title_sort	future trends in the pharmacogenomics of brain disorders and dementia: influence of apoe and cyp2d6 variants
description	About 80% of functional genes in the human genome are expressed in the brain and over 1,200 different genes have been associated with the pathogenesis of CNS disorders and dementia. Pharmacogenetic studies of psychotropic drug response have focused on determining the relationship between variations in specific candidate genes and the positive and adverse effects of drug treatment. Approximately, 18% of neuroleptics are substrates of CYP1A2 enzymes, 40% of CYP2D6, and 23% of CYP3A4; 24% of antidepressants are substrates of CYP1A2 enzymes, 5% of CYP2B6, 38% of CYP2C19, 85% of CYP2D6, and 38% of CYP3A4; 7% of benzodiazepines are substrates of CYP2C19 enzymes, 20% of CYP2D6, and 95% of CYP3A4. 10-20% of Western populations are defective in genes of the CYP superfamily; and the pharmacogenomic response of psychotropic drugs also depends on genetic variants associated with dementia. Prospective studies with anti-dementia drugs or with multifactorial strategies have revealed that the therapeutic response to conventional drugs in Alzheimer’s disease is genotype-specific. The disease-modifying effects (cognitive performance, biomarker modification) of therapeutic intervention are APOE-dependent, with APOE-4 carriers acting as the worst responders (APOE-3/3 > APOE-3/4 > APOE-4/4). APOE-CYP2D6 interactions also influence the therapeutic outcome in patients with dementia.
publisher	MDPI
publishDate	2010
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034082/
_version_	1612093469203890176

Future Trends in the Pharmacogenomics of Brain Disorders and Dementia: Influence of APOE and CYP2D6 Variants

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