The CALHM1 P86L polymorphism is a genetic modifier of age at onset in 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, MARIA;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.

2010-01-01

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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.