title: Cathepsin D (C224T) polymorphism in sporadic and genetic Creutzfeldt-Jakob disease.
abstract: Accumulation of cathepsin D immunoreactive lysosomes correlates with tissue pathology in sporadic Creutzfeldt-Jakob disease (CJD) brains. The C-to-T transition within exon 2 of the cathepsin D (CTSD) gene is associated with altered enzymatic activity. Possession of the TT genotype is a risk factor for variant CJD. To verify the association between the CTSD position 224T allele and the risk for and survival in sporadic and genetic CJD, we genotyped 540 sporadic, 101 genetic CJD, and 723 control individuals. Genotype data and duration of illness were compared using multiple logistic regression and Kruskal-Wallis test. Multivariate survival analysis was performed using Cox's regression model. The distribution of CTSD position 224 alleles was approximately the same in all groups. We observed a trend for shorter survival in sporadic CJD patients harboring the T allele at position 224 of the CTSD gene in particular in sporadic CJD patients with the prion protein gene position 129 MM genotype. We conclude that the CTSD position 224 polymorphism alone is not a significant risk or disease-modifying factor in sporadic or genetic CJD.
authors: Institute of Neurology, Medical University of Vienna, Austria.
authors: Gabor G
authors: GG
authors: Kovacs
authors: Pascual
authors: P
authors: Sanchez-Juan
authors: Thomas
authors: T
authors: Ströbel
authors: Maaike
authors: M
authors: Schuur
authors: Anna
authors: A
authors: Poleggi
authors: Sara
authors: S
authors: Nocentini
authors: Claudia
authors: C
authors: Giannattasio
authors: Girma
authors: G
authors: Belay
authors: Matthew
authors: M
authors: Bishop
authors: Sabina
authors: S
authors: Capellari
authors: Piero
authors: P
authors: Parchi
authors: Ellen
authors: E
authors: Gelpi
authors: Aniko
authors: A
authors: Gal
authors: Agnes
authors: A
authors: Bakos
authors: Maria J
authors: MJ
authors: Molnar
authors: Uta
authors: U
authors: Heinemann
authors: Inga
authors: I
authors: Zerr
authors: Richard S G
authors: RS
authors: Knight
authors: Eva
authors: E
authors: Mitrova
authors: Cornelia
authors: C
authors: van Duijn
authors: Herbert
authors: H
authors: Budka
mesh_terms: D000328:Adult; D000368:Aged; D002402:Cathepsin D / Q000235:genetics*; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics* / Q000401:mortality; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D002402:Cathepsin D