TY - JOUR
T1 - The influence of PRNP polymorphisms on human prion disease susceptibility
T2 - an update
AU - Kobayashi, Atsushi
AU - Teruya, Kenta
AU - Matsuura, Yuichi
AU - Shirai, Tsuyoshi
AU - Nakamura, Yoshikazu
AU - Yamada, Masahito
AU - Mizusawa, Hidehiro
AU - Mohri, Shirou
AU - Kitamoto, Tetsuyuki
N1 - Funding Information:
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.).
Publisher Copyright:
© 2015, Springer-Verlag Berlin Heidelberg.
PY - 2015/8/25
Y1 - 2015/8/25
N2 - 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.
AB - 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.
KW - Creutzfeldt–Jakob disease
KW - PRNP
KW - Polymorphism
KW - Prion
UR - http://www.scopus.com/inward/record.url?scp=84937815223&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937815223&partnerID=8YFLogxK
U2 - 10.1007/s00401-015-1447-7
DO - 10.1007/s00401-015-1447-7
M3 - Review article
C2 - 26022925
AN - SCOPUS:84937815223
SN - 0001-6322
VL - 130
SP - 159
EP - 170
JO - Acta Neuropathologica
JF - Acta Neuropathologica
IS - 2
ER -
