The genetics of susceptibility to variant Creutzfeldt-Jakob disease

The emergence of bovine spongiform encephalopathy (BSE) in cattle and, subsequently, its transmission to humans resulting in variant Creutzfeldt-Jakob disease (vCJD) in the UK has proved to be one of the major public health scares of the century. The oral route of infection, the long incubation period, and the incredible resistance of the transmissible infectious agent to various forms of decontamination poses unique challenges. Fortunately, despite extensive exposure of the UK population to contaminated meat, the size of the vCJD epidemic that has emerged since its initial detection is relatively low (225 worldwide). An explanation for this disparity is as yet incomplete, but the development of the disease is likely influenced by a number of factors including physical properties of the infectious agent, environmental factors such as the route and amount of exposure and individual susceptibility factors. This review focuses on current knowledge of the genetic factors that undoubtedly play a major role in influencing the development of vCJD. In terms of genetic susceptibility, the best characterised is the common single nucleotide polymorphism at codon 129 of the human prion protein gene (PRNP). Moreover, several other polymorphisms and mutations have been identified that may affect susceptibility as well as other important disease characteristics such as the highly variable prion disease incubation period.