{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:57:53Z","timestamp":1790996273814,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/00659"],"award-info":[{"award-number":["PI20\/00659"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d'Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","award":["#BP00176"],"award-info":[{"award-number":["#BP00176"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>\u03b1\u2010Synuclein (<jats:italic>SNCA<\/jats:italic>) gene hypomethylation was reported in idiopathic Parkinson's disease (iPD). Based on a high clinical resemblance between iPD and leucine\u2010rich repeat kinase 2 (LRRK2)\u2010driven Parkinson's disease (L2PD), we investigated the epigenetic status of <jats:italic>SNCA<\/jats:italic> in an extensive LRRK2 clinical cohort from Spain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed the methylation levels of 23 CpG sites in the <jats:italic>SNCA<\/jats:italic> promoter region using peripheral blood DNA from L2PD patients (n\u2009=\u2009151), LRRK2 nonmanifesting carriers (n\u2009=\u200955), iPD patients (n\u2009=\u2009115), and healthy control subjects (n\u2009=\u2009154) (total: N\u2009=\u2009475).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with control subjects, we found significant <jats:italic>SNCA<\/jats:italic> hypomethylation in 11 of 23 CpGs in L2PD (48%), whereas 22 CpGs (96%) were hypomethylated in iPD. In line with a healthy status, asymptomatic mutation carriers had similar <jats:italic>SNCA<\/jats:italic> methylation profiles to control subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study shows for the first time that <jats:italic>SNCA<\/jats:italic> hypomethylation occurs in patients with L2PD. Further studies addressing <jats:italic>SNCA<\/jats:italic> methylation status in additional worldwide LRRK2 cohorts are warranted. \u00a9 2024 The Author(s). <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.30094","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T03:23:48Z","timestamp":1734924228000},"page":"550-555","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["\u03b1\u2010Synuclein Gene Hypomethylation in <scp>LRRK2<\/scp> Parkinson's Disease Patients"],"prefix":"10.1002","volume":"40","author":[{"given":"Lorena","family":"de Mena","sequence":"first","affiliation":[{"name":"Laboratory of Parkinson's and Other Movement Disorders Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer  Barcelona Spain"},{"name":"Institut de Neuroci\u00e8ncies, Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillem","family":"Par\u00e9s","sequence":"additional","affiliation":[{"name":"Laboratory of Parkinson's and Other Movement Disorders Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer  Barcelona Spain"},{"name":"Institut de Neuroci\u00e8ncies, Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Garrido","sequence":"additional","affiliation":[{"name":"Institut de Neuroci\u00e8ncies, Universitat de Barcelona  Barcelona Spain"},{"name":"Parkinson's Disease and Movement Disorders Unit, Neurology Service Hospital Cl\u00ednic de Barcelona  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas CB06\/05\/0018\u2010ISCIII  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F.","family":"Pilco\u2010Janeta","sequence":"additional","affiliation":[{"name":"Institut de Neuroci\u00e8ncies, Universitat de Barcelona  Barcelona Spain"},{"name":"Parkinson's Disease and Movement Disorders Unit, Neurology Service Hospital Cl\u00ednic de Barcelona  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas CB06\/05\/0018\u2010ISCIII  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manel","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratory of Parkinson's and Other Movement Disorders Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer  Barcelona Spain"},{"name":"Institut de Neuroci\u00e8ncies, Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesica","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Laboratory of Parkinson's and Other Movement Disorders Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer  Barcelona Spain"},{"name":"Institut de Neuroci\u00e8ncies, Universitat de Barcelona  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas CB06\/05\/0018\u2010ISCIII  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3781-0854","authenticated-orcid":false,"given":"Eduardo","family":"Tolosa","sequence":"additional","affiliation":[{"name":"Laboratory of Parkinson's and Other Movement Disorders Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer  Barcelona Spain"},{"name":"Institut de Neuroci\u00e8ncies, Universitat de Barcelona  Barcelona Spain"},{"name":"Parkinson's Disease and Movement Disorders Unit, Neurology Service Hospital Cl\u00ednic de Barcelona  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas CB06\/05\/0018\u2010ISCIII  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