5e624c83-2f60-4c71-8ac1-d8fabaafde3e
title
Polymorphisms in the  prion protein gene  and in the  doppel gene  increase susceptibility for Creutzfeldt-Jakob disease.
e1ba8a65-52ee-4ca2-876c-c43e8ac8134d
abstract
The  prion protein gene  ( PRNP ) plays a central role in the origin of Creutzfeldt-Jakob disease (CJD), but there is growing interest in other polymorphisms that may be involved in CJD. Polymorphisms upstream of  PRNP  that may modulate the  prion protein  production as well as polymorphisms in the  prion-like doppel gene  ( PRND ) have been studied, with inconsistent findings. We investigated the role of a single-nucleotide polymorphism ( SNP 1368 ) located upstream of  PRNP  and three polymorphisms in  PRND  ( T26M ,  P56L  and  T174M ) in CJD. The study included a population-based sample of 52 patients with sporadic CJD and 250 controls. We analysed our data as single markers and haplotypes. Further, we conducted a meta-analysis on  PRND   T174M  comparing the data of the four studies conducted to date. For  SNP 1368  and  PRNP   M129V , we found significant evidence for linkage disequilibrium. No evidence was found for a relation of  SNP 1368  to CJD independent of  PRNP   M129V . We further found a significant increased prevalence of M homozygotes at  PRND   T174M  among sporadic CJD patients, when adjusting the analyses for the other genotypes. In the haplotype analyses, the association was strongest for persons homozygous for  PRNP   129M  and  PRND   174M  (odds ratio 4.35, 95% confidence interval 1.05-8.09; P=0.04). The meta-analysis on the  PRND   T174M  polymorphism did not show a consistent effect across studies, raising the question as to whether  PRND   174M  is causally related to CJD, or whether the  PRND  allele is in linkage disequilibrium with another polymorphism related to CJD.