Genomics of Dementia:APOE- andCYP2D6-Related Pharmacogenetics

Autor: Adam McKay, Iván Tellado, Valter Lombardi, Iván Carrera, Rocío Martínez, Lucía Fernández-Novoa, Ramón Cacabelos, Masatoshi Takeda, Jerzy Leszek, Juan C. Carril, Lola Corzo
Rok vydání: 2012
Předmět:
Zdroj: International Journal of Alzheimer's Disease, Vol 2012 (2012)
International Journal of Alzheimer's Disease
ISSN: 2090-0252
2090-8024
Popis: Dementia is a major problem of health in developed societies. Alzheimer’s disease (AD), vascular dementia, and mixed dementia account for over 90% of the most prevalent forms of dementia. Both genetic and environmental factors are determinant for the phenotypic expression of dementia. AD is a complex disorder in which many different gene clusters may be involved. Most genes screened to date belong to different proteomic and metabolomic pathways potentially affecting AD pathogenesis. The ε4 variant of theAPOEgene seems to be a major risk factor for both degenerative and vascular dementia. Metabolic factors, cerebrovascular disorders, and epigenetic phenomena also contribute to neurodegeneration. Five categories of genes are mainly involved in pharmacogenomics: genes associated with disease pathogenesis, genes associated with the mechanism of action of a particular drug, genes associated with phase I and phase II metabolic reactions, genes associated with transporters, and pleiotropic genes and/or genes associated with concomitant pathologies. TheAPOEandCYP2D6genes have been extensively studied in AD. The therapeutic response to conventional drugs in patients with AD is genotype specific, withCYP2D6-PMs,CYP2D6-UMs, andAPOE-4/4carriers acting as the worst responders.APOEandCYP2D6may cooperate, as pleiotropic genes, in the metabolism of drugs and hepatic function. The introduction of pharmacogenetic procedures into AD pharmacological treatment may help to optimize therapeutics.
Databáze: OpenAIRE
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