Limits...
Alzheimer's disease and HLA-A2: linking neurodegenerative to immune processes through an in silico approach.

Cifuentes RA, Murillo-Rojas J - Biomed Res Int (2014)

Bottom Line: It has been suggested a modifier effect on the risk that depends on genetic loadings.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.

View Article: PubMed Central - PubMed

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

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.

Show MeSH

Related in: MedlinePlus

Forest plots of studies that relate HLA-A2 and AD. (a) Shows the effect summary OR (pooled OR) that takes into account all the studies. (b) Shows the pooled OR when each one of the studies was removed (sensitivity analysis).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4150521&req=5

fig1: Forest plots of studies that relate HLA-A2 and AD. (a) Shows the effect summary OR (pooled OR) that takes into account all the studies. (b) Shows the pooled OR when each one of the studies was removed (sensitivity analysis).

Mentions: From Europe, North-America and Asia, nineteen studies with data from case-control studies (2619 cases and 3878 controls) fitted the selection criteria; detailed information on the 185 articles that were excluded is given in the supplementary Table S1 in the Supplementary Material available online at http://dx.doi.org/10.1155/2014/791238. 17 of the included studies were from Caucasians [11, 12, 21–35] and 2 from Asians [13, 36]; see Table 1. Regarding the meta-analysis, the HLA-A2 did not have a specific behavior of risk or of protection with a pooled OR of 1.11, 95%CI: 0.98 to 1.24 (QP value 0.02). None of the articles included in the meta-analysis showed a significant OR lesser than one, but in contrast four studies showed a significant OR higher than one. In the same line, exclusion of one study by means of the sensitivity analysis led in some cases to significant risk behavior of the HLA-A2 but never to a significant protective behavior (Figure 1).


Alzheimer's disease and HLA-A2: linking neurodegenerative to immune processes through an in silico approach.

Cifuentes RA, Murillo-Rojas J - Biomed Res Int (2014)

Forest plots of studies that relate HLA-A2 and AD. (a) Shows the effect summary OR (pooled OR) that takes into account all the studies. (b) Shows the pooled OR when each one of the studies was removed (sensitivity analysis).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150521&req=5

fig1: Forest plots of studies that relate HLA-A2 and AD. (a) Shows the effect summary OR (pooled OR) that takes into account all the studies. (b) Shows the pooled OR when each one of the studies was removed (sensitivity analysis).
Mentions: From Europe, North-America and Asia, nineteen studies with data from case-control studies (2619 cases and 3878 controls) fitted the selection criteria; detailed information on the 185 articles that were excluded is given in the supplementary Table S1 in the Supplementary Material available online at http://dx.doi.org/10.1155/2014/791238. 17 of the included studies were from Caucasians [11, 12, 21–35] and 2 from Asians [13, 36]; see Table 1. Regarding the meta-analysis, the HLA-A2 did not have a specific behavior of risk or of protection with a pooled OR of 1.11, 95%CI: 0.98 to 1.24 (QP value 0.02). None of the articles included in the meta-analysis showed a significant OR lesser than one, but in contrast four studies showed a significant OR higher than one. In the same line, exclusion of one study by means of the sensitivity analysis led in some cases to significant risk behavior of the HLA-A2 but never to a significant protective behavior (Figure 1).

Bottom Line: It has been suggested a modifier effect on the risk that depends on genetic loadings.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.

View Article: PubMed Central - PubMed

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

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.

Show MeSH
Related in: MedlinePlus