2026-05-07T08:14:53Zhttps://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 Walter, Caroline Riess, Olaf Roos, Raymund A. C. Nielsen, Jørgen E. Craufurd, David Cubo Delgado, Esther REGISTRY investigators of the European Huntington's Disease Network 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