Regulatory sequences of the PRNP gene influence susceptibility to sporadic Creutzfeldt-Jakob disease

The prion diseases are fatal neurodegenerative disorders that afflict both humans and animals. They comprise kuru, Creutzfeldt-Jakob disease (CJD), Gerstmman-Straussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI). Both GSS, FFI and approximately 10% of CJD cases are genetically linked disorders, whereas 90% of CJD cases are not associated with mutations in the PRNP coding region, therefore other factors must be involved in pathogenesis of these forms of CJD. There is strong evidence that in transgenic mice the level of PrP gene expression influences the initiation and progression of the prion diseases. Moreover, in in vitro experiments demonstrated that mutations in the regulatory region of PRNP gene altered gene expression, therefore it may be expected that PrP expression level influences the susceptibility to CJD. In order to investigate whether single nucleotide polymorphisms within regulatory region of PRNP may modulate genetic susceptibility to sporadic CJD we examined an association of the C/G polymorphism at position -101 with the sCJD. In our study -101G polymorphism is over-represented among sCJD PRNP codon 129M/V cases compared with the control group. Our data suggest that polymorphism at position -101 in the regulatory region of PRNP may be a risk factor for sCJD among codon 129 heterozygotes.