Evidence of the association of BIN1 and PICALM with the AD risk in contrasting European populations

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URI: http://hdl.handle.net/10902/6222
ISSN: 0197-4580
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Autoría
Lambert, Jean-Charles; Zelenika, Diana; Hiltunen, Mikko; Chouraki, Vincent; Combarros Pascual, OnofreAutoridad Unican; Bullido, María Jesús; Tognoni, Gloria; Fiévet, Nathalie; Boland, Anne; Arosio, Beatrice; Coto García, Elicer; Zompo, Maria del; Mateo Fernández, José Ignacio; Frank García, Ana; Helisalmi, Seppo; Porcellini, Elisa; Pilotto, Alberto; Forti, Paola; Ferri, Raffaele; [et al.]
Fecha
2011-04
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© Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Neurobiology of Aging. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neurobiology of Aging. 2011 Apr;32(4):756.e11-5. doi: 10.1016/j.neurobiolaging.2010.11.022.
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Neurobiology of Aging. 2011 Apr;32(4):756.e11-5
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Elsevier
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Resumen/Abstract
Recent genome-wide association studies have identified five loci (BIN1, 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 three contrasting European populations (from Finland, Italy and Spain). Since CLU and CR1 had already been analyzed in these populations, we restricted our investigation to BIN1, EXO2CL3 and PICALM. In a total of 2,816 AD cases and 2,706 controls, we unambiguously replicated the association of rs744373 (for BIN1) and rs541458 (for PICALM) polymorphisms with the AD risk (OR=1.26, 95% CI [1.15-1.38], p=2.9x10-7, and OR=0.80, 95% CI [0.74-0.88], p=4.6x10-7, respectively). In a meta-analysis, rs597668 (EXOC3L2) was also associated with the AD risk, albeit to a lesser extent (OR=1.19, 95% CI [1.06-1.32], p=2.0x10-3). However, this signal did not appear to be independent of APOE. In conclusion, we confirmed that BIN1 and PICALM are genetic determinants of AD, whereas the potential involvement of EXOC3L2 requires further investigation.
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