治疗阿尔茨海默病的药物基因组学中的多效性和混杂性及其相关危险因素

IF 0.6 Q4 CLINICAL NEUROLOGY

Future Neurology Pub Date : 2018-02-05 DOI:10.2217/FNL-2017-0038

R. Cacabelos

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引用次数: 14

摘要

阿尔茨海默病患者目前是多种药物的消费者，药物相互作用的风险很高。抗痴呆药物和其他治疗痴呆相关血管风险因素的药物发挥多效性作用，这些作用受到不同基因产物的混杂调节。这篇综述的目的是强调药物遗传学相关基因（即致病基因、机制基因、代谢基因、转运蛋白基因和多效性基因）作为阿尔茨海默病治疗反应的主要决定因素的影响。与广泛或中间代谢者相比，携带较差或超快基因表型的患者在药物疗效和安全性方面表现出更多的不规则特征。与脂质代谢相关的基因的多态性变体影响对低脂药物的治疗反应。了解这些影响对于优化痴呆症的综合治疗非常有用。

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Pleiotropy and promiscuity in pharmacogenomics for the treatment of Alzheimer's disease and related risk factors

Patients with Alzheimer's disease are current consumers of polypharmacy with a high risk for drug–drug interactions. Antidementia drugs and other pharmacological treatments for vascular risk factors associated with dementia exert pleiotropic effects which are promiscuously regulated by different gene products. The aim of this review is to highlight the influence of genes involved in pharmacogenetics (i.e., pathogenic, mechanistic, metabolic, transporter and pleiotropic genes) as major determinants of response to treatment in Alzheimer's disease. Patients harboring poor or ultrarapid geno-phenotypes display more irregular profiles in drug efficacy and safety than extensive or intermediate metabolizers. Polymorphic variants of genes associated with lipid metabolism influence the therapeutic response to hypolipemic agents. Understanding these effects is very useful for optimizing polytherapy in dementia.

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来源期刊

Future Neurology CLINICAL NEUROLOGY-

CiteScore

2.10

自引率

0.00%

发文量

期刊介绍： The neurological landscape is changing rapidly. From the technological perspective, advanced molecular approaches and imaging modalities have greatly increased our understanding of neurological disease, with enhanced prospects for effective treatments in common but very serious disorders such as stroke, epilepsy, multiple sclerosis and Parkinson’s disease. Nevertheless, at the same time, the healthcare community is increasingly challenged by the rise in neurodegenerative diseases consequent upon demographic changes in developed countries.