Human prion diseases are fatal neurodegenerative disorders that are 
characterized by spongiform changes, astrogliosis, and the accumulation of an 
abnormal prion protein (PrP(Sc)). Approximately 10%-15% of human prion diseases 
are familial variants that are caused by pathogenic mutations in the prion 
protein gene (PRNP). Point mutations or the insertions of one or more copies of 
a 24 bp repeat are associated with familial human prion diseases including 
familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker 
syndrome, and fatal familial insomnia. These mutations vary significantly in 
frequency between countries. Here, we compare the frequency of PRNP mutations 
between European countries and East Asians. Associations between single 
nucleotide polymorphisms (SNPs) of several candidate genes including PRNP and 
CJD have been reported. The SNP of PRNP at codon 129 has been shown to be 
associated with sporadic, iatrogenic, and variant CJD. The SNPs of several genes 
other than PRNP have been showed contradictory results. Case-control studies and 
genome-wide association studies have also been performed to identify candidate 
genes correlated with variant and/or sporadic CJD. This review provides a 
general overview of the genetic mutations and polymorphisms that have been 
analyzed in association with human prion diseases to date.