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

Atsushi Kobayashi1, Kenta Teruya, Yuichi Matsuura

  • 1Department of Neurological Science, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan, kobayashi@vetmed.hokudai.ac.jp.

Acta Neuropathologica
|May 30, 2015
PubMed

Insights

Human prion disease susceptibility is influenced by PRNP gene variations. Specific PRNP genotypes like 129M/M increase risk for sporadic and variant Creutzfeldt-Jakob disease, while others offer partial protection or predisposition.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • The human PRNP gene encodes the prion protein.
  • Two common PRNP polymorphisms, methionine (M)/valine (V) at codon 129 and glutamic acid (E)/lysine (K) at codon 219, are known to influence prion disease susceptibility.
  • Previous studies indicated 129M/M homozygosity is associated with sporadic and variant Creutzfeldt-Jakob disease (CJD), and 219E/K heterozygosity is absent in sporadic CJD patients.

Purpose of the Study:

  • To review recent advances in understanding the complex relationships between PRNP gene polymorphisms and prion disease susceptibility.
  • To highlight novel findings from experimental transmission studies and global surveillance data.

Main Methods:

  • Review of existing literature and surveillance data on prion diseases.
  • Analysis of experimental transmission studies.
  • Correlation of PRNP genotypes with different prion disease phenotypes.

Main Results:

  • 129M/M homozygosity is overrepresented in sporadic and variant CJD.
  • 219E/K heterozygosity, while conferring resistance to sporadic CJD, does not fully protect against acquired or genetic prion diseases.
  • 129M/V heterozygosity predisposes to genetic CJD associated with PRNP codon 180 mutation.

Conclusions:

  • The influence of PRNP polymorphisms on prion disease susceptibility is more intricate than previously understood.
  • PRNP genotype interactions with different prion disease types (sporadic, acquired, genetic) require further investigation.
  • Ongoing research continues to refine our understanding of genetic risk factors for prion diseases.

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