Journal
NEUROBIOLOGY OF AGING
Volume 32, Issue 4, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2010.11.022
Keywords
BIN1; PICALM; EXOC3L2; APOE; Alzheimer; Risk; GWA; Association; Polymorphism
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Funding
- Kuopio University Hospital [5772708]
- Nordic Centre of Excellence in Neurodegeneration
- Italian Ministry of Research and University
- Fondazione del Monte di Bologna e Ravenna
- Italian Ministry of Health [REPS-2006-7-334858, PS 39]
- Monzino Foundation
- Ministerio de Educacion y Ciencia
- Ministerio de Sanidad y Consumo (Instituto de Salud Carlos III)
- Fundacion Ramon Areces
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Recent genome-wide association studies have identified 5 loci (BIM, CLU, CR1, EXOC3L2, and PICALM) as genetic determinants of Alzheimer's disease (AD). We attempted to confirm the association between these genes and the AD risk in 3 contrasting European populations (from Finland, Italy, and Spain). Because CLU and CRI had already been analyzed in these populations, we restricted our investigation to BIN1, EXO2CL3, and PICALM. In a total of 2816 AD cases and 2706 controls, we unambiguously replicated the association of rs744373 (for BIN1) and rs541458 (for PICALM) polymorphisms with the AD risk (odds ratio [OR] = 1.26, 95% confidence interval [Cl] [1.15-1.38], p = 2.9 X 10(-7), and OR = 0.80, 95% CI [0.74-0.88], p = 4.6 X 10(-7), respectively). In a meta-analysis, rs597668 (EXOC3L2) was also associated with the AD risk, albeit to a lesser extent (OR = 1.19, 95% Cl [1.06-1.32], p = 2.0 X 10(-3)). However, this signal did not appear to be independent of APOE. In conclusion, we confirmed that BIN! and PICALM are genetic determinants of AD, whereas the potential involvement of EXOC3L2 requires further investigation. (C) 2011 Elsevier Inc. All rights reserved.
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