The CALHM1 P86L Polymorphism is a Genetic Modifier of Age at Onset in Alzheimer's Disease: a Meta-Analysis Study

• Published in: Journal of Alzheimer's disease 2010-01, Vol.22 (1), p.247-255
• Main Authors: Lambert, Jean-Charles, Sleegers, Kristel, González-Pérez, Antonio, Ingelsson, Martin, Beecham, Gary W., Hiltunen, Mikko, Combarros, Onofre, Bullido, Maria J., Brouwers, Nathalie, Bettens, Karolien, Berr, Claudine, Pasquier, Florence, Richard, Florence, DeKosky, Steven T., Hannequin, Didier, Haines, Jonathan L., Tognoni, Gloria, Fiévet, Nathalie, Dartigues, Jean-François, Tzourio, Christophe, Engelborghs, Sebastiaan, Arosio, Beatrice, Coto, Elicer, De Deyn, Peter, Del Zompo, Maria, Mateo, Ignacio, Boada, Merce, Antunez, Carmen, Lopez-Arrieta, Jesus, Epelbaum, Jacques, Schjeide, Brit-Maren Michaud, Frank-Garcia, Ana, Giedraitis, Vilmentas, Helisalmi, Seppo, Porcellini, Elisa, Pilotto, Alberto, Forti, Paola, Ferri, Raffaele, Delepine, Marc, Zelenika, Diana, Lathrop, Mark, Scarpini, Elio, Siciliano, Gabriele, Solfrizzi, Vincenzo, Sorbi, Sandro, Spalletta, Gianfranco, Ravaglia, Giovanni, Valdivieso, Fernando, Vepsäläinen, Saila, Alvarez, Victoria, Bosco, Paolo, Mancuso, Michelangelo, Panza, Francesco, Nacmias, Benedetta, Bossù, Paola, Hanon, Olivier, Piccardi, Paola, Annoni, Giorgio, Mann, David, Marambaud, Philippe, Seripa, Davide, Galimberti, Daniela, Tanzi, Rudolph E, Bertram, Lars, Lendon, Corinne, Lannfelt, Lars, Licastro, Federico, Campion, Dominique, Pericak-Vance, Margaret A., Soininen, Hilkka, Van Broeckhoven, Christine, Alpérovitch, Annick, Ruiz, Agustin, Kamboh, M. Ilyas, Amouyel, Philippe
• Format: Article
• Language: English
• Subjects: Age at onset; Age of Onset; Aged; Aged, 80 and over; Alleles; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Alzheimer's disease; apolipoprotein E; Apolipoprotein E4 - genetics; Apolipoprotein E4 - metabolism; Calcium Channels - genetics; Calcium Channels - metabolism; CALHM1; Case-Control Studies; Female; Humans; Male; MEDICIN; MEDICINE; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Middle Aged; polymorphism; Polymorphism, Genetic - genetics
• ISSN: 1387-2877; 1875-8908; 1875-8908
• DOI: 10.3233/JAD-2010-100933

The only established genetic determinant of non-Mendelian forms of Alzheimer's disease (AD) is the ε4 allele of the apolipoprotein E gene (APOE). Recently, it has been reported that the P86L polymorphism of the calcium homeostasis modulator 1 gene (CALHM1) is associated with the risk of developing AD. In order to independently assess this association, we performed a meta-analysis of 7,873 AD cases and 13,274 controls of Caucasian origin (from a total of 24 centers in Belgium, Finland, France, Italy, Spain, Sweden, the UK, and the USA). Our results indicate that the CALHM1 P86L polymorphism is likely not a genetic determinant of AD but may modulate age of onset by interacting with the effect of the ε4 allele of the APOE gene.