Prion protein codon 129 genotype prevalence is altered in primary progressive aphasia.
The prion protein (PrP) is central to the prion diseases, although a role in other neurodegenerative diseases has been postulated. A common polymorphism (Met or Val) at codon 129 of the PrP gene (PRNP) features prominently in the risk and phenotype, of prion disease, and an abnormality in its distribution frequency may signal a role for PrP in other diseases. We conducted a case-control study to compare the PRNP codon 129 genotype distribution in Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and primary progressive aphasia (PPA), including 281 AD, 256 ALS, 39 PPA, and 415 healthy control subjects. Statistical analysis was applied to determine the presence or absence of disease-specific genotype associations. The distribution of codon 129 genotypes was similar among healthy control, AD, and ALS subjects, although the heterozygous state was significantly overrepresented (age-adjusted odds ratio, 8.47) in PPA, a rare condition of unknown cause. Although these findings do not entirely exclude a role for PrP in AD or ALS, they do not support the codon 129 genotype as a risk factor for either disease. However, the strong association between heterozygosity and PPA raises new questions about its cause and the role of PrP in other neurodegenerative diseases.
Li
Xiaohong
X
Department of Neurology, Pritzker School of Medicine and Center for Comprehensive Care and Research on Memory Disorders, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA.
Rowland
Lewis P
LP
Mitsumoto
Hiroshi
H
Przedborski
Serge
S
Bird
Thomas D
TD
Schellenberg
Gerard D
GD
Peskind
Elaine
E
Johnson
Nancy
N
Siddique
Teepu
T
Mesulam
M-Marsel
MM
Weintraub
Sandra
S
Mastrianni
James A
JA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics; D018888:Aphasia, Primary Progressive / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D015995:Prevalence; D011328:Prions / Q000235:genetics*
D011328:Prions