The influence of PRNP polymorphisms on human prion disease susceptibility: an update

Atsushi Kobayashi, Kenta Teruya, Yuichi Matsuura, Tsuyoshi Shirai, Yoshikazu Nakamura, Masahito Yamada, Hidehiro Mizusawa, Shirou Mohri, Tetsuyuki Kitamoto

Research output: Contribution to journalReview articlepeer-review

50 Citations (Scopus)


Two normally occurring polymorphisms of the human PRNP gene, methionine (M)/valine (V) at codon 129 and glutamic acid (E)/lysine (K) at codon 219, can affect the susceptibility to prion diseases. It has long been recognized that 129M/M homozygotes are overrepresented in sporadic Creutzfeldt–Jakob disease (CJD) patients and variant CJD patients, whereas 219E/K heterozygotes are absent in sporadic CJD patients. In addition to these pioneering findings, recent progress in experimental transmission studies and worldwide surveillance of prion diseases have identified novel relationships between the PRNP polymorphisms and the prion disease susceptibility. For example, although 219E/K heterozygosity confers resistance against the development of sporadic CJD, this genotype is not entirely protective against acquired forms (iatrogenic CJD and variant CJD) or genetic forms (genetic CJD and Gerstmann–Sträussler–Scheinker syndrome) of prion diseases. In addition, 129M/V heterozygotes predispose to genetic CJD caused by a pathogenic PRNP mutation at codon 180. These findings show that the effects of the PRNP polymorphisms may be more complicated than previously thought. This review aims to summarize recent advances in our knowledge about the influence of the PRNP polymorphisms on the prion disease susceptibility.

Original languageEnglish
Pages (from-to)159-170
Number of pages12
JournalActa neuropathologica
Issue number2
Publication statusPublished - 2015 Aug 25


  • Creutzfeldt–Jakob disease
  • PRNP
  • Polymorphism
  • Prion

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'The influence of PRNP polymorphisms on human prion disease susceptibility: an update'. Together they form a unique fingerprint.

Cite this