2026-04-30T01:39:33Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/87702024-03-08T01:05:14Zcom_10259_4219com_10259_5086com_10259_2604col_10259_4220

Metzger, Silke 57304b9b-2794-4bce-8399-b5b59533b6a6 600 Walter, Caroline 16527cd0-df06-4d8f-a120-21b9b2d1bc07 600 Riess, Olaf b5b5e0cf-0a11-4988-af4d-021f8a0f38d8 600 Roos, Raymund A. C. d3cb78a0-e6cb-4438-8037-c1a5c4f9a889 600 Nielsen, Jørgen E. 20ce1cf7-8110-495b-893d-4b15bf7feb65 600 Craufurd, David 605623d4-aa75-4669-b629-dc3fba8f82b8 600 Cubo Delgado, Esther 131 600 0000-0003-0018-1182 REGISTRY investigators of the European Huntington's Disease Network e1e01874-0f5b-4401-94c7-c848893348be 600 2024-03-07T08:39:31Z 2024-03-07T08:39:31Z 2013-07 http://hdl.handle.net/10259/8770 10.1371/journal.pone.0068951 1932-6203 The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis. The study was supported by the GeNeMove Network for hereditary movement disorders (01GM0603). application/pdf eng Public Library of Science PLoS ONE. 2013, V. 8, n. 7, e68951 https://doi.org/10.1371/journal.pone.0068951 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Sistema nervioso-Enfermedades Medicina Nervous system-Diseases Medicine The V471A Polymorphism in Autophagy-Related Gene ATG7 Modifies Age at Onset Specifically in Italian Huntington Disease Patients info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion PLoS ONE 8 7 THUMBNAIL Metzger-po_2013.pdf.jpg Metzger-po_2013.pdf.jpg IM Thumbnail image/jpeg 3915 https://riubu.ubu.es/bitstream/10259/8770/4/Metzger-po_2013.pdf.jpg 2ec65389e1dc4542a8b40873a8948dea MD5 4 LICENSE license.txt license.txt text/plain; charset=utf-8 999 https://riubu.ubu.es/bitstream/10259/8770/3/license.txt b295bcbce42e2caabeb0c623d3860c06 MD5 3 CC-LICENSE license_rdf license_rdf application/rdf+xml; charset=utf-8 908 https://riubu.ubu.es/bitstream/10259/8770/2/license_rdf 0175ea4a2d4caec4bbcc37e300941108 MD5 2 ORIGINAL Metzger-po_2013.pdf Metzger-po_2013.pdf application/pdf 207491 https://riubu.ubu.es/bitstream/10259/8770/1/Metzger-po_2013.pdf 1b6b6d5cb8ab94864783d1d1ef188d91 MD5 1 10259/8770 oai:riubu.ubu.es:10259/8770 2024-03-08 02:05:14.769 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es 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