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BioMed Research International
Volume 2014, Article ID 791238, 9 pages
http://dx.doi.org/10.1155/2014/791238
Review Article

Alzheimer’s Disease and HLA-A2: Linking Neurodegenerative to Immune Processes through an In Silico Approach

Area of Basic Sciences, Faculty of Medicine, Universidad Militar Nueva Granada, Bogotá, Colombia

Received 22 January 2014; Accepted 8 July 2014; Published 17 August 2014

Academic Editor: Francesco Pappalardo

Copyright © 2014 Ricardo A. Cifuentes and Juan Murillo-Rojas. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

There is a controversial relationship between HLA-A2 and Alzheimer’s disease (AD). It has been suggested a modifier effect on the risk that depends on genetic loadings. Thus, the aims of this study were to evaluate this relationship and to reveal genes associated with both concepts the HLA-A gene and AD. Consequently, we did first a classical systematic review and a meta-analysis of case-control studies. Next, by means of an in silico approach, we used experimental knowledge of protein-protein interactions to evaluate the top ranked genes shared by both concepts, previously found through text mining. The meta-analysis did not show a significant pooled OR (1.11, 95% CI: 0.98 to 1.24 in Caucasians), in spite of the fact that four of the included studies had a significant OR > 1 and none of them a significant OR < 1. In contrast, the in silico approach retrieved nonrandomly shared genes by both concepts (P = 0.02), which additionally encode truly interacting proteins. The network of proteins encoded by APP, ICAM-1, ITGB2, ITGAL, SELP, SELL, IL2, IL1B, CD4, and CD8A linked immune to neurodegenerative processes and highlighted the potential roles in AD pathogenesis of endothelial regulation, infectious diseases, specific antigen presentation, and HLA-A2 in maintaining synapses.