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.
*Institute of Neurology, Medical University of Vienna, and Austrian REFERENCE Centre for Human Prion Diseases, Vienna, Austria
†Institute for Formation and Research of the Fundación “Marqués de Valdecilla” (IFIMAV), Santander
‡Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain
§Department of Neurology
∥Department of Genetic Epidemiology of the Erasmus Medical Center, Rotterdam; The Netherlands
¶Department of “Cell Biology and Neurosciences”, Istituto Superiore di Sanità, Rome
††Dipartimento di Scienze Neurologiche, Universitá di Bologna, Bologna, Italy
♯Department of Prion Diseases, Institute of Preventive and Clinical Medicine, Research Base of Slovak Medical University, Bratislava, Slovak Republic
**National CJD Surveillance Unit, Bryan Matthews Building, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK
‡‡Centre for Molecular Neurology, Department of Neurology, Semmelweis University
§§Microbiological Research Group, National Centre for Epidemiology, Budapest, Hungary
∥∥Department of Neurology, National TSE REFERENCE Centre, Göttingen, Germany
Sources of Funding: Supported by EUROCJD collaboration funded by NeuroPrion and partially by the Robert Koch-Institute through funds of the Federal Ministry of Health (grant No. 1369-341 to IZ) and was partially supported by a collaborative agreement Italy-USA (530F/0F28). The Dutch Creutzfeldt-Jakob Disease Surveillance is funded by the Dutch Ministry of Health, Welfare, and Sports.
Reprints: Herbert Budka, MD, MScDhc, Institute of Neurology, Medical University Vienna, AKH 4J, POB 48, A-1097 Wien, Austria (e-mail: email@example.com).
Received for publication November 19, 2008
accepted April 7, 2009