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.
The CALHM1 P86L polymorphism is a genetic modifier of age at onsetin Alzheimer's disease: a meta-analysis study / Lambert JC; Sleegers K; González-Pérez A; Ingelsson M; Beecham GW; Hiltunen M; Combarros O; Bullido MJ; Brouwers N; Bettens K; Berr C; Pasquier F; Richard F; Dekosky ST; Hannequin D; Haines JL; Tognoni G; Fiévet N; Dartigues JF; Tzourio C; Engelborghs S; Arosio B; Coto E; De Deyn P; Del Zompo M; Mateo I; Boada M; Antunez C; Lopez-Arrieta J; Epelbaum J; Schjeide BM; Frank-Garcia A; Giedraitis V; Helisalmi S; Porcellini E; Pilotto A; Forti P; Ferri R; Delepine M; Zelenika D; Lathrop M; Scarpini E; Siciliano G; Solfrizzi V; Sorbi S; Spalletta G; Ravaglia G; Valdivieso F; Vepsäläinen S; Alvarez V; Bosco P; Mancuso M; Panza F; Nacmias B; Bossù P; Hanon O; Piccardi P; Annoni G; Mann D; Marambaud P; Seripa D; Galimberti D; Tanzi RE; Bertram L; Lendon C; Lannfelt L; Licastro F; Campion D; Pericak-Vance MA; Soininen H; Van Broeckhoven C; Alpérovitch A; Ruiz A; Kamboh MI; Amouyel P.. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - STAMPA. - 22:(2010), pp. 247-255. [10.3233/JAD-2010-100933]
The CALHM1 P86L polymorphism is a genetic modifier of age at onsetin Alzheimer's disease: a meta-analysis study.
SORBI, SANDRO;NACMIAS, BENEDETTA;
2010
Abstract
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.
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