Opportunities in pharmacogenomics for the treatment of Alzheimer's disease

被引：18

作者：

Cacabelos, Ramon ^{[1
,2
]}

Torrellas, Clara ^{[1
,2
]}

Carrera, Ivan ^{[1
,2
]}

机构：

[1] Camilo Jose Cela Univ, Madrid 28692, Spain

[2] EuroEspes Biomed Res Ctr, Inst Med Sci & Genom Med, Corunna, Spain

来源：

FUTURE NEUROLOGY | 2015年 / 10卷 / 03期

关键词：

Alzheimer's disease; ABCB1; APOE; CYP2C9; CYP2C19; CYP2D6; epigenetic drugs; pharmacogenomics; TOMM40;

D O I：

10.2217/FNL.15.12

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

In Alzheimer's disease (AD), approximately 10-20% of direct costs are associated with pharmacological treatment. Pharmacogenomics account for 30-90% variability in pharmacokinetics and pharmacodynamics. Genes potentially involved in the pharmacogenomics outcome include pathogenic, mechanistic, metabolic, transporter and pleiotropic genes. Over 75% of the Caucasian population is defective for the CYP2D6+ 2C9+ 2C19 cluster. Polymorphic variants in the APOE-TOMM40 region influence AD pharmacogenomics. APOE-4 carriers are the worst responders and APOE-3 carriers are the best responders to conventional treatments. TOMM40 poly T-S/S carriers are the best responders, VL/VL and S/VL carriers are intermediate responders and L/L carriers are the worst responders. The haplotype 4/4-L/L is probably responsible for early onset of the disease, a faster cognitive decline and a poor response to different treatments.

引用

页码：229 / 252

页数：24

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