APOE-TOMM40 in the Pharmacogenomics of DementiaRamón Cacabelos1*, Dmitry Goldgaber2, Alexander Vostrov2, Hideyuki Matsuki2, Clara Torrellas1, Dolores Corzo1, Juan Carlos Carril1 and Allen D Roses3
- *Corresponding Author:
- Prof. Dr. Ramón Cacabelos
Chair of Genomic Medicine
Camilo José Cela University, Castillo de Alarcón
49 Urb. Villafranca del CastilloVillanueva de la Cañada 28692-Madrid, Spain
Tel: +34 91 815 3131
E-mail: [email protected]
Received date: April 24, 2014; Accepted date: June 27, 2014; Published date: July 04, 2014
Citation: Cacabelos R, Goldgaber D, Vostrov A, Matsuki H, Torrellas C, et al. (2014) APOE-TOMM40 in the Pharmacogenomics of Dementia. J Pharmacogenomics Pharmacoproteomics 5:135. doi: 10.4172/2153-0645.1000135
Copyright: © 2014 Cacabelos R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Polymorphic variants present in the APOE-TOMM40 region (19q13.2) are implicated in Alzheimer’s disease (AD) and have been shown to modify disease risk, age at onset of symptoms, and the therapeutic response to conventional drugs. We have investigated the structure of the APOE-TOMM40 region and the influence of APOE and TOMM40 poly T variants (rs10524523) in the therapeutic response to a multifactorial treatment in 920 Spanish patients with AD. The frequencies of TOMM40 poly T genotypes were: 18.37% S/S, 7.83% S/L, 38.80% S/VL, 1.52% L/L, 7.17% L/VL, and 26.31% VL/VL. The most frequent APOE-TOMM40 associations were as follows: 82% APOE-3/3 with S/S, 63% with S/VL, and 40% with VL/VL; 90% APOE-3/4 with S/L, 57% with L/VL, and 43% with VL/VL; and 100% APOE-4/4 with L/L. Globally, the response rate was about 59%, with no difference between females and males. APOE-4 carriers were found to be the worst responders (45-56%) whereas APOE-3/3 carriers were the best responders (70%) for a transient period of cognitive improvement (<12 m). Among TOMM40 variants, S/S carriers were the best responders (70%), followed by S/VL (61%), VL/VL (57%), and L/VL carriers (51%). The worst responders were those patients harboring the L/L genotype (35%). Therefore, specific APOE-TOMM40 poly T variants exert a powerful influence on the therapeutic response to conventional treatments in AD.