{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:40:20Z","timestamp":1792798820517,"version":"4.5.0"},"reference-count":44,"publisher":"BMJ","issue":"7","funder":[{"name":"Research Committee of Surveillance and Infection Control of Prion Disease, the Ministry of Health, Labour and Welfare of the Japanese government","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}],"id":[{"id":"https:\/\/ror.org\/03mwa7s65","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>No studies have assessed the independent association of methionine homozygosity at codon 129 with the susceptibility to prion diseases, controlling for the effects of the codon 219 polymorphisms and other potential confounders, using a large-scale population-based dataset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a case-control study using a Japanese nationwide surveillance database for prion diseases. The main exposure was methionine homozygosity at codon 129, and the outcome was development of prion diseases. Multivariable logistic regression models were employed for specific disease subtypes (sporadic Creutzfeldt-Jakob disease (CJD), genetic CJD and Gerstmann-Str\u00e4ussler-Scheinker disease (GSS)).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 5461 patients registered in the database, 2440 cases and 796 controls remained for the analysis. The cases comprised 1676 patients with sporadic CJD (69%), 649 with genetic CJD (27%) and 115 with GSS (5%). For patients with methionine homozygosity, potential risk for occurring prion diseases: adjusted OR (95% CI) was 2.21 (1.46 to 3.34) in sporadic CJD, 0.47 (0.32 to 0.68) in genetic CJD and 0.3 (0.17 to 0.55) in GSS. Among patients with specific prion protein abnormalities, the potential risk was 0.27 (0.17 to 0.41) in genetic CJD with 180 Val\/Ile, 1.66 (0.65 to 5.58) in genetic CJD with 200 Glu\/Lys, 3.97 (1.2 to 24.62) in genetic CJD with 232 Met\/Arg and 0.71 (0.34 to 1.67) in GSS with 102 Pro\/Leu.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Methionine homozygosity at codon 129 was predisposing to sporadic CJD, but protective against genetic CJD and GSS, after adjustment for codon 219 polymorphism effect. However, the impacts differed completely among patients with specific prion protein abnormalities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jnnp-2021-328720","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T06:35:37Z","timestamp":1655188537000},"page":"779-784","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Methionine homozygosity for PRNP polymorphism and susceptibility to human prion diseases"],"prefix":"10.1136","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1050-2699","authenticated-orcid":false,"given":"Koki","family":"Kosami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2660-530X","authenticated-orcid":false,"given":"Ryusuke","family":"Ae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1126-3776","authenticated-orcid":false,"given":"Tsuyoshi","family":"Hamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1226-2425","authenticated-orcid":false,"given":"Nobuo","family":"Sanjo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Tsukamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuyuki","family":"Kitamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2416-5662","authenticated-orcid":false,"given":"Masahito","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidehiro","family":"Mizusawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosikazu","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"2023051710501221000_93.7.779.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81163-0"},{"key":"2023051710501221000_93.7.779.2","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181cd7374"},{"key":"2023051710501221000_93.7.779.3","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1098\/rstb.1994.0034","article-title":"Human prion diseases with variant prion protein","volume":"343","author":"Kitamoto","year":"1994","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"2023051710501221000_93.7.779.4","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/0169-328X(95)00034-P","article-title":"New variant prion protein in a Japanese family with Gerstmann-Str\u00e4ussler syndrome","volume":"30","author":"Furukawa","year":"1995","journal-title":"Brain Res Mol Brain Res"},{"key":"2023051710501221000_93.7.779.5","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199908)46:2<224::AID-ANA12>3.0.CO;2-W"},{"key":"2023051710501221000_93.7.779.6","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh249"},{"key":"2023051710501221000_93.7.779.7","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1447-7"},{"key":"2023051710501221000_93.7.779.8","doi-asserted-by":"publisher","DOI":"10.1038\/352340a0"},{"key":"2023051710501221000_93.7.779.9","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1212\/WNL.44.12.2347","article-title":"Molecular genetics of prion diseases in France. 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