RT info:eu-repo/semantics/article
T1 The V471A Polymorphism in Autophagy-Related Gene ATG7 Modifies Age at Onset Specifically in Italian Huntington Disease Patients
A1 Metzger, Silke
A1 Walter, Caroline
A1 Riess, Olaf
A1 Roos, Raymund A. C.
A1 Nielsen, Jørgen E.
A1 Craufurd, David
A1 Cubo Delgado, Esther
A1 REGISTRY investigators of the European Huntington's Disease Network
K1 Sistema nervioso-Enfermedades
K1 Nervous system-Diseases
K1 Medicina
K1 Medicine
AB 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.
PB Public Library of Science
YR 2013
FD 2013-07
LK http://hdl.handle.net/10259/8770
UL http://hdl.handle.net/10259/8770
LA eng
NO The study was supported by the GeNeMove Network for hereditary movement disorders (01GM0603).
DS Repositorio Institucional de la Universidad de Burgos
RD 22-dic-2024