{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:17:35Z","timestamp":1792113455548,"version":"4.4.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T00:00:00Z","timestamp":1457568000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T00:00:00Z","timestamp":1457568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Parkinson's Disease"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in glucocerebrosidase (<jats:italic>GBA<\/jats:italic>) are a common risk factor for Parkinson's disease (PD). The scavenger receptor class B member 2 (<jats:italic>SCARB2<\/jats:italic>) gene encodes a receptor responsible for the transport of glucocerebrosidase (GCase) to the lysosome. Two common SNPs in linkage disequilibrium with <jats:italic>SCARB2<\/jats:italic>, rs6812193 and rs6825004, have been associated with PD and Lewy Body Disease in genome-wide association studies. Whether these SNPs are associated with altered glucocerebrosidase enzymatic activity is unknown. Our objective was to determine whether <jats:italic>SCARB2<\/jats:italic> SNPs are associated with PD and with reduced GCase activity. The <jats:italic>GBA<\/jats:italic> gene was fully sequenced, and the <jats:italic>LRRK2<\/jats:italic> G2019S and <jats:italic>SCARB2<\/jats:italic> rs6812193 and rs6825004 SNPs were genotyped in 548 PD patients and 272 controls. GCase activity in dried blood spots was measured by tandem mass spectrometry. We tested the association between <jats:italic>SCARB2<\/jats:italic> genotypes and PD risk in regression models adjusted for gender, age, and <jats:italic>LRRK2<\/jats:italic> G2019S and <jats:italic>GBA<\/jats:italic> mutation status. We compared GCase activity between participants with different genotypes at rs6812193 and rs6825004. Genotype at rs6812193 was associated with PD status. PD cases were less likely to carry the T allele than the C allele (OR=0.71; <jats:italic>P<\/jats:italic>=0.004), but GCase enzymatic activity was similar across rs6812193 genotypes (C\/C: 11.88\u2009\u03bcmol\/l\/h; C\/T: 11.80\u2009\u03bcmol\/l\/h; T\/T: 12.02\u2009\u03bcmol\/l\/h; <jats:italic>P<\/jats:italic>=0.867). Genotype at rs6825004 was not associated with either PD status or GCase activity. In conclusion, our results support an association between <jats:italic>SCARB2<\/jats:italic> genotype at rs6812193 and PD, but suggest that the increased risk is not mediated by GCase activity.<\/jats:p>","DOI":"10.1038\/npjparkd.2016.4","type":"journal-article","created":{"date-parts":[[2016,3,9]],"date-time":"2016-03-09T21:20:22Z","timestamp":1457558422000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["SCARB2 variants and glucocerebrosidase activity in Parkinson\u2019s disease"],"prefix":"10.1038","volume":"2","author":[{"given":"Roy N","family":"Alcalay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oren A","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavlina","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Oliva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokui Kate","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl H","family":"Waters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Fahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Un Jung","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Liong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blair","family":"Ford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Mazzoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy A","family":"Rouleau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy K","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen S","family":"Marder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziv","family":"Gan-Or","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,3,10]]},"reference":[{"key":"BFnpjparkd20164_CR1","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1056\/NEJMoa0901281","volume":"361","author":"E Sidransky","year":"2009","unstructured":"Sidransky, E. et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N. Engl. J. Med. 361, 1651\u20131661 (2009).","journal-title":"N. Engl. J. Med."},{"key":"BFnpjparkd20164_CR2","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1093\/brain\/awp044","volume":"132","author":"J Neumann","year":"2009","unstructured":"Neumann, J. et al. Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease. Brain 132, 1783\u20131794 (2009).","journal-title":"Brain"},{"key":"BFnpjparkd20164_CR3","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.jns.2014.01.022","volume":"339","author":"M Zeigler","year":"2014","unstructured":"Zeigler, M. et al. A novel SCARB2 mutation in progressive myoclonus epilepsy indicated by reduced beta-glucocerebrosidase activity. J. Neurol. Sci. 339, 210\u2013213 (2014).","journal-title":"J. Neurol. 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Chem."}],"container-title":["npj Parkinson's Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/npjparkd20164.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/npjparkd20164","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/npjparkd20164.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T12:10:15Z","timestamp":1672834215000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/npjparkd20164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,10]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,1]]}},"alternative-id":["BFnpjparkd20164"],"URL":"https:\/\/doi.org\/10.1038\/npjparkd.2016.4","relation":{},"ISSN":["2373-8057"],"issn-type":[{"value":"2373-8057","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,10]]},"assertion":[{"value":"23 October 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"R.N.A. is supported by the Parkinson\u2019s Disease Foundation, the National Institutes of Health (K02NS080915, and UL1 TR000040, formerly the National Center for Research Resources, Grant Number UL1 RR024156), the Smart Foundation and the Brookdale Foundation. He received consultation fees from Genzyme\/Sanofi and Prophase. Ms P.W. and Drs P.O. and X.K.Z. are employees of Genzyme\/Sanofi. Dr S.F. reports Consulting and Advisory Board Membership with honoraria: Merz Pharma, Genervon Biotechnology; PixarBio; Lundbeck Pharma. Grants\/Research Support: 69Genervon Biotechnology. U.K. reports research grants from NIH, the Michael J Fox Foundation, and the Parkinson Disease Foundation, not related to the submitted work. He consults for Caremark\/CVS. S.K. has received funding from the National Institutes of Health: NINDS #K08 NS083738 (principal investigator), the Louis V. Gerstner Jr. Scholar Award, the Parkinson\u2019s Disease Foundation, the American Parkinson\u2019s Disease Association, the International Essential Tremor Foundation, NIEHS Pilot Grant ES009089 (principal investigator), and the Smart Foundation. K.S.M. reports grants from NIH [#NS036630 (PI), 1UL1 RR024156-01(Director PCIR), PO412196- G (Co-I), and PO412196-G (Co-I)], grants from steering committee for U01NS052592, grants from the Parkinson\u2019s Disease Foundation, and grants from Michael J Fox Foundation, outside the submitted work. The remaining authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16004"}}