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Pharmacogenetics of Vascular Risk Factors in Alzheimer’s Disease
Alzheimer’s disease (AD) is a polygenic/complex disorder in which genomic, epigenomic, cerebrovascular, metabolic, and environmental factors converge to define a progressive neurodegenerative phenotype. Pharmacogenetics is a major determinant of therapeutic outcome in AD. Different categories of gen...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872077/ https://www.ncbi.nlm.nih.gov/pubmed/29301387 http://dx.doi.org/10.3390/jpm8010003 |
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author | Cacabelos, Ramón Meyyazhagan, Arun Carril, Juan C. Cacabelos, Pablo Teijido, Óscar |
author_facet | Cacabelos, Ramón Meyyazhagan, Arun Carril, Juan C. Cacabelos, Pablo Teijido, Óscar |
author_sort | Cacabelos, Ramón |
collection | PubMed |
description | Alzheimer’s disease (AD) is a polygenic/complex disorder in which genomic, epigenomic, cerebrovascular, metabolic, and environmental factors converge to define a progressive neurodegenerative phenotype. Pharmacogenetics is a major determinant of therapeutic outcome in AD. Different categories of genes are potentially involved in the pharmacogenetic network responsible for drug efficacy and safety, including pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes. However, most drugs exert pleiotropic effects that are promiscuously regulated for different gene products. Only 20% of the Caucasian population are extensive metabolizers for tetragenic haplotypes integrating CYP2D6-CYP2C19-CYP2C9-CYP3A4/5 variants. Patients harboring CYP-related poor (PM) and/or ultra-rapid (UM) geno-phenotypes display more irregular profiles in drug metabolism than extensive (EM) or intermediate (IM) metabolizers. Among 111 pentagenic (APOE-APOB-APOC3-CETP-LPL) haplotypes associated with lipid metabolism, carriers of the H26 haplotype (23-TT-CG-AG-CC) exhibit the lowest cholesterol levels, and patients with the H104 haplotype (44-CC-CC-AA-CC) are severely hypercholesterolemic. Furthermore, APOE, NOS3, ACE, AGT, and CYP variants influence the therapeutic response to hypotensive drugs in AD patients with hypertension. Consequently, the implementation of pharmacogenetic procedures may optimize therapeutics in AD patients under polypharmacy regimes for the treatment of concomitant vascular disorders. |
format | Online Article Text |
id | pubmed-5872077 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-58720772018-03-30 Pharmacogenetics of Vascular Risk Factors in Alzheimer’s Disease Cacabelos, Ramón Meyyazhagan, Arun Carril, Juan C. Cacabelos, Pablo Teijido, Óscar J Pers Med Review Alzheimer’s disease (AD) is a polygenic/complex disorder in which genomic, epigenomic, cerebrovascular, metabolic, and environmental factors converge to define a progressive neurodegenerative phenotype. Pharmacogenetics is a major determinant of therapeutic outcome in AD. Different categories of genes are potentially involved in the pharmacogenetic network responsible for drug efficacy and safety, including pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes. However, most drugs exert pleiotropic effects that are promiscuously regulated for different gene products. Only 20% of the Caucasian population are extensive metabolizers for tetragenic haplotypes integrating CYP2D6-CYP2C19-CYP2C9-CYP3A4/5 variants. Patients harboring CYP-related poor (PM) and/or ultra-rapid (UM) geno-phenotypes display more irregular profiles in drug metabolism than extensive (EM) or intermediate (IM) metabolizers. Among 111 pentagenic (APOE-APOB-APOC3-CETP-LPL) haplotypes associated with lipid metabolism, carriers of the H26 haplotype (23-TT-CG-AG-CC) exhibit the lowest cholesterol levels, and patients with the H104 haplotype (44-CC-CC-AA-CC) are severely hypercholesterolemic. Furthermore, APOE, NOS3, ACE, AGT, and CYP variants influence the therapeutic response to hypotensive drugs in AD patients with hypertension. Consequently, the implementation of pharmacogenetic procedures may optimize therapeutics in AD patients under polypharmacy regimes for the treatment of concomitant vascular disorders. MDPI 2018-01-03 /pmc/articles/PMC5872077/ /pubmed/29301387 http://dx.doi.org/10.3390/jpm8010003 Text en © 2018 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 (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Cacabelos, Ramón Meyyazhagan, Arun Carril, Juan C. Cacabelos, Pablo Teijido, Óscar Pharmacogenetics of Vascular Risk Factors in Alzheimer’s Disease |
title | Pharmacogenetics of Vascular Risk Factors in Alzheimer’s Disease |
title_full | Pharmacogenetics of Vascular Risk Factors in Alzheimer’s Disease |
title_fullStr | Pharmacogenetics of Vascular Risk Factors in Alzheimer’s Disease |
title_full_unstemmed | Pharmacogenetics of Vascular Risk Factors in Alzheimer’s Disease |
title_short | Pharmacogenetics of Vascular Risk Factors in Alzheimer’s Disease |
title_sort | pharmacogenetics of vascular risk factors in alzheimer’s disease |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872077/ https://www.ncbi.nlm.nih.gov/pubmed/29301387 http://dx.doi.org/10.3390/jpm8010003 |
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