Meta-analysis of genetic variability in the beta-amyloid production, aggregation and degradation metabolic pathways and the risk of Alzheimer's disease.

Abstract:

BACKGROUND:Variants in genes encoding enzymes involved in production, aggregation or degradation of beta-amyloid are potential risk factors for sporadic Alzheimer's disease (AD). METHODS:Meta-analyses on AD association with BACE1 exon 5, BACE1 intron 5, FE65 intron 13, CYP46 intron 2, alpha(1)-antichymotrypsine Ala17Thr, bleomycin hydrolase I443V, lectin-like oxidized low-density lipoprotein receptor (OLR1) 3'-UTR (+1071) and (+1073), and very-low-density lipoprotein receptor (VLDLR) 5'-UTR (CGG-repeat) polymorphisms. RESULTS:In BACE1 exon 5, genotype CC+CT acts as a protective factor in Apolipoprotein E (ApoE) epsilon 4 carriers [odds ratio (OR) = 0.57; 95% confidence interval (CI): 0.38-0.88], and as a risk factor in ApoE epsilon 4 non-carriers (OR = 1.33; 95% CI: 1.00-1.78). OLR1 3'-UTR (+1073) allele C is associated with increased risk (OR = 1.23; 95% CI: 1.01-1.50). VLDLR 5'-UTR genotype 2 is associated with increased risk (OR = 1.70; 95% CI: 1.09-2.63) in the Asian population and is protective (OR = 0.48; 95% CI: 0.26-0.86) in the non-Asian population. Other studied polymorphisms are not associated with AD. CONCLUSIONS:The overall impact on AD risk of the genes for which meta-analyses are now available is rather limited. Additional meta-analyses of other different genes encoding for A beta production, aggregation and degradation mediators might help in determining the risk profile for AD.

journal_name

Acta Neurol Scand

authors

Llorca J,Rodríguez-Rodríguez E,Dierssen-Sotos T,Delgado-Rodríguez M,Berciano J,Combarros O

doi

10.1111/j.1600-0404.2007.00899.x

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

1-14

issue

1

eissn

0001-6314

issn

1600-0404

pii

ANE899

journal_volume

117

pub_type

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