Acta Neuropathologica

, Volume 130, Issue 2, pp 159–170 | Cite as

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 KitamotoEmail author


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.


Creutzfeldt–Jakob disease Prion PRNP Polymorphism 



We thank members of the Creutzfeldt–Jakob Disease Surveillance Committee in Japan, Creutzfeldt–Jakob disease specialists in the prefectures, and Creutzfeldt–Jakob disease patients and families for providing important clinical information. We thank Y. Ishikawa, H. Kudo, M. Yamamoto, and A. Yamazaki for their excellent technical assistance, and B. Bell for critical review of the manuscript. This study was supported by Grants-in-Aid from the Ministry of Health, Labor and Welfare of Japan (A.K., Y.N., M.Y., H.M., S.M. and T.K.), Grants-in-Aid for Scientific Research from JSPS (A.K. and T.K.), the Platform for Drug Design, Informatics, and Structural Lifescience (PDIS) (T.S.), a grant from MEXT for the Joint Research Program of the Research Center for Zoonosis Control, Hokkaido University (T.K.), and a Grant-in-Aid for Scientific Research on Innovative Areas from MEXT (T.K.).

Conflict of interest

The authors declare that they have no conflicting interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Atsushi Kobayashi
    • 1
    • 8
  • Kenta Teruya
    • 2
  • Yuichi Matsuura
    • 3
  • Tsuyoshi Shirai
    • 4
  • Yoshikazu Nakamura
    • 5
  • Masahito Yamada
    • 6
  • Hidehiro Mizusawa
    • 7
  • Shirou Mohri
    • 1
  • Tetsuyuki Kitamoto
    • 1
    Email author
  1. 1.Department of Neurological ScienceTohoku University Graduate School of MedicineSendaiJapan
  2. 2.Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
  3. 3.Influenza and Prion Disease Research CenterNational Institute of Animal HealthTsukubaJapan
  4. 4.Department of Computer BioscienceNagahama Institute of Bio-Science and TechnologyNagahamaJapan
  5. 5.Department of Public HealthJichi Medical UniversityShimotsukeJapan
  6. 6.Department of Neurology and Neurobiology of AgingKanazawa University Graduate School of Medical ScienceKanazawaJapan
  7. 7.National Center HospitalNational Center of Neurology and PsychiatryKodairaJapan
  8. 8.Laboratory of Comparative Pathology, Graduate School of Veterinary MedicineHokkaido UniversitySapporoJapan

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