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

被引：66

作者：

Kobayashi, Atsushi ^{[1
,8
]}

Teruya, Kenta ^{[2
]}

Matsuura, Yuichi ^{[3
]}

Shirai, Tsuyoshi ^{[4
]}

Nakamura, Yoshikazu ^{[5
]}

Yamada, Masahito ^{[6
]}

Mizusawa, Hidehiro ^{[7
]}

Mohri, Shirou ^{[1
]}

Kitamoto, Tetsuyuki ^{[1
]}

机构：

[1] Tohoku Univ, Grad Sch Med, Dept Neurol Sci, Aoba Ku, Sendai, Miyagi 9808575, Japan

[2] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Kita Ku, Kyoto 6038334, Japan

[3] Natl Inst Anim Hlth, Influenza & Prion Dis Res Ctr, Tsukuba, Ibaraki 3050856, Japan

[4] Nagahama Inst Biosci & Technol, Dept Comp Biosci, Nagahama 5260829, Japan

[5] Jichi Med Univ, Dept Publ Hlth, Shimotsuke 3290498, Japan

[6] Kanazawa Univ, Grad Sch Med Sci, Dept Neurol & Neurobiol Aging, Kanazawa, Ishikawa 9208640, Japan

[7] Natl Ctr Hosp, Natl Ctr Neurol & Psychiat, Kodaira, Tokyo 1878511, Japan

[8] Hokkaido Univ, Grad Sch Vet Med, Lab Comparat Pathol, Kita Ku, Sapporo, Hokkaido 0600818, Japan

来源：

ACTA NEUROPATHOLOGICA | 2015年 / 130卷 / 02期

关键词：

Creutzfeldt-Jakob disease; Prion; PRNP; Polymorphism; CREUTZFELDT-JAKOB-DISEASE; PROTEASE-SENSITIVE PRIONOPATHY; WILD-TYPE; STRAIN VARIATION; CODON; 129; TRANSMISSION PROPERTIES; BLOOD-TRANSFUSION; E200K MUTATION; NMR STRUCTURE; VARIANT;

D O I：

10.1007/s00401-015-1447-7

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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-Straussler-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.

引用

页码：159 / 170

页数：12

共 87 条

[21] Variably Protease-Sensitive Prionopathy: a Novel Disease of the Prion Protein [J].