NR APAD
AU Vollmert,C.; Xiang,W.; Windl,O.; Rosenberger,A.; Zerr,I.; Wichmann,H.E.; Bickeböller,H.; Poser,S.; Illig,T.; Kretzschmar,H.A.
TI Several SNPs in the PRNP gene are associated with sporadic Creutzfeldt-Jakob disease
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - DG-21
PT Konferenz-Poster
AB
The etiology of sporadic Creutzfeldt-Jakob disease (sCJD), the most common form of the human prion disease, remains obscure. The sole described genetic factor influencing the susceptibility for this disease is a common polymorphism in the coding region of the PRNP gene at the codon 129 (PRNP_129). However, further major genetic predisposing factors for sCJD might still be unknown. The aim of this study was the identification of informative polymorphisms additional to PRNP_129 in candidate genes using an association study in a large cohort.
By means of MALDI-TOF MS technique (MassArray, Sequenom, San Diego), we genotyped 9 SNPs in the PRNP locus and 8 SNPs in the PRNP-like protein gene (PRND) as well as three further genes, which are known to be differentially expressed during prion infection or were suggested to be involved in prion diseases by other studies. Genotyping was performed in 584 sCJD cases and 749 healthy controls matched for age and gender which were taken from a population based study performed in the city and region of Augsburg, Germany (KORA Survey 2000). Aside from the PRNP_129 polymorphism we further detected a highly significant association between sCJD and 6 additional SNPs of the PRNP locus. The role of these SNPs as possible additional risk factors to the PRNP_129 polymorphism was evaluated. Furthermore, common haplotypes which were overrepresented in patients with sCJD were identified. The SNPs analysed in the other candidate genes did not show significant association with sCJD, and therefore, a predisposing role of these SNPs to sCJD seems improbable. Using this unique patient sample, we could evaluate published data in PRNP and other genes which were derived from much smaller cohorts and produced conflicting data.
AD Xiang, O. Windl, H.A. Kretzschmar, Institute of Neuropathology, Ludwig-Maximilians-University Munich, Germany; C. Vollmert, H.E. Wichmann, T. Illig, Institute of Epidemiology, GSF-Research Center of Environment and Health, Neuherberg, Germany; I. Zerr, S. Poser, Department of Neurology, University of Göttingen, Göttingen, Germany; W. A. Rosenberger, H. Bickeböller, Department of Genetic Epidemiology, University of Göttingen, Göttingen, Germany
SP englisch
PO Deutschland