Is M129V of PRNP gene associated with Alzheimer's disease? A case-control study and a meta-analysis.
The methionine/valine (M/V) polymorphism at codon 129 within the prion protein gene (PRNP) represents a known risk factor for Creutzfeldt-Jakob disease (CJD). Few authors reported also the effects of this polymorphism on the risk of Alzheimer's disease (AD), although with controversial results. To better clarify this issue, we performed a novel case-control study and a meta-analysis of published association studies between PRNP and AD. Our findings argue against PRNP as a susceptibility gene for developing AD in the Italian population but support the hypothesis that the V allele influences cognitive performances. The meta-analysis, revealed that Caucasian subjects homozygous at codon 129 had a 1.3-fold increased risk [95% CI: 1.0-1.6, p = 0.05] of developing AD compared to heterozygous individuals. We also observed that MM genotype and M allele represent a risk factor for AD, independently from the ethnic background, providing a significant but modest association between this polymorphism and AD.
Del Bo
Roberto
R
Dino Ferrari Centre, Department of Neurological Sciences, University of Milan and Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Padiglione Ponti, Milano, Italy. roberto.delbo@unimi.it
Scarlato
Marina
M
Ghezzi
Serena
S
Martinelli-Boneschi
Filippo
F
Fenoglio
Chiara
C
Galimberti
Gloria
G
Galbiati
Sara
S
Virgilio
Roberta
R
Galimberti
Daniela
D
Ferrarese
Carlo
C
Scarpini
Elio
E
Bresolin
Nereo
N
Comi
Giacomo Pietro
GP
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D000682:Amyloid / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D003071:Cognition / Q000502:physiology; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors / Q000235:genetics*
D000682:Amyloid; D001057:Apolipoproteins E; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors; D004247:DNA