| Literature DB >> 19734903 |
Jean-Charles Lambert1, Simon Heath, Gael Even, Dominique Campion, Kristel Sleegers, Mikko Hiltunen, Onofre Combarros, Diana Zelenika, Maria J Bullido, Béatrice Tavernier, Luc Letenneur, Karolien Bettens, Claudine Berr, Florence Pasquier, Nathalie Fiévet, Pascale Barberger-Gateau, Sebastiaan Engelborghs, Peter De Deyn, Ignacio Mateo, Ana Franck, Seppo Helisalmi, Elisa Porcellini, Olivier Hanon, Marian M de Pancorbo, Corinne Lendon, Carole Dufouil, Céline Jaillard, Thierry Leveillard, Victoria Alvarez, Paolo Bosco, Michelangelo Mancuso, Francesco Panza, Benedetta Nacmias, Paola Bossù, Paola Piccardi, Giorgio Annoni, Davide Seripa, Daniela Galimberti, Didier Hannequin, Federico Licastro, Hilkka Soininen, Karen Ritchie, Hélène Blanché, Jean-François Dartigues, Christophe Tzourio, Ivo Gut, Christine Van Broeckhoven, Annick Alpérovitch, Mark Lathrop, Philippe Amouyel.
Abstract
The gene encoding apolipoprotein E (APOE) on chromosome 19 is the only confirmed susceptibility locus for late-onset Alzheimer's disease. To identify other risk loci, we conducted a large genome-wide association study of 2,032 individuals from France with Alzheimer's disease (cases) and 5,328 controls. Markers outside APOE with suggestive evidence of association (P < 10(-5)) were examined in collections from Belgium, Finland, Italy and Spain totaling 3,978 Alzheimer's disease cases and 3,297 controls. Two loci gave replicated evidence of association: one within CLU (also called APOJ), encoding clusterin or apolipoprotein J, on chromosome 8 (rs11136000, OR = 0.86, 95% CI 0.81-0.90, P = 7.5 x 10(-9) for combined data) and the other within CR1, encoding the complement component (3b/4b) receptor 1, on chromosome 1 (rs6656401, OR = 1.21, 95% CI 1.14-1.29, P = 3.7 x 10(-9) for combined data). Previous biological studies support roles of CLU and CR1 in the clearance of beta amyloid (Abeta) peptide, the principal constituent of amyloid plaques, which are one of the major brain lesions of individuals with Alzheimer's disease.Entities:
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Year: 2009 PMID： 19734903 DOI： 10.1038/ng.439
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330