The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients.
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...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0068951 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850162055840006144 |
|---|---|
| author | Silke Metzger Carolin Walter Olaf Riess Raymund A C Roos Jørgen E Nielsen David Craufurd REGISTRY Investigators of the European Huntington’s Disease Network Huu Phuc Nguyen |
| author_facet | Silke Metzger Carolin Walter Olaf Riess Raymund A C Roos Jørgen E Nielsen David Craufurd REGISTRY Investigators of the European Huntington’s Disease Network Huu Phuc Nguyen |
| author_sort | Silke Metzger |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9713d43f9dc645bfbdf87cb9a5a9c8f3 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-9713d43f9dc645bfbdf87cb9a5a9c8f32025-08-20T02:22:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6895110.1371/journal.pone.0068951The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients.Silke MetzgerCarolin WalterOlaf RiessRaymund A C RoosJørgen E NielsenDavid CraufurdREGISTRY Investigators of the European Huntington’s Disease NetworkHuu Phuc NguyenThe 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.https://doi.org/10.1371/journal.pone.0068951 |
| spellingShingle | Silke Metzger Carolin Walter Olaf Riess Raymund A C Roos Jørgen E Nielsen David Craufurd REGISTRY Investigators of the European Huntington’s Disease Network Huu Phuc Nguyen The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients. PLoS ONE |
| title | The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients. |
| title_full | The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients. |
| title_fullStr | The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients. |
| title_full_unstemmed | The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients. |
| title_short | The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients. |
| title_sort | v471a polymorphism in autophagy related gene atg7 modifies age at onset specifically in italian huntington disease patients |
| url | https://doi.org/10.1371/journal.pone.0068951 |
| work_keys_str_mv | AT silkemetzger thev471apolymorphisminautophagyrelatedgeneatg7modifiesageatonsetspecificallyinitalianhuntingtondiseasepatients AT carolinwalter thev471apolymorphisminautophagyrelatedgeneatg7modifiesageatonsetspecificallyinitalianhuntingtondiseasepatients AT olafriess thev471apolymorphisminautophagyrelatedgeneatg7modifiesageatonsetspecificallyinitalianhuntingtondiseasepatients AT raymundacroos thev471apolymorphisminautophagyrelatedgeneatg7modifiesageatonsetspecificallyinitalianhuntingtondiseasepatients AT jørgenenielsen thev471apolymorphisminautophagyrelatedgeneatg7modifiesageatonsetspecificallyinitalianhuntingtondiseasepatients AT davidcraufurd thev471apolymorphisminautophagyrelatedgeneatg7modifiesageatonsetspecificallyinitalianhuntingtondiseasepatients AT registryinvestigatorsoftheeuropeanhuntingtonsdiseasenetwork thev471apolymorphisminautophagyrelatedgeneatg7modifiesageatonsetspecificallyinitalianhuntingtondiseasepatients AT huuphucnguyen thev471apolymorphisminautophagyrelatedgeneatg7modifiesageatonsetspecificallyinitalianhuntingtondiseasepatients AT silkemetzger v471apolymorphisminautophagyrelatedgeneatg7modifiesageatonsetspecificallyinitalianhuntingtondiseasepatients AT carolinwalter v471apolymorphisminautophagyrelatedgeneatg7modifiesageatonsetspecificallyinitalianhuntingtondiseasepatients AT olafriess v471apolymorphisminautophagyrelatedgeneatg7modifiesageatonsetspecificallyinitalianhuntingtondiseasepatients AT raymundacroos v471apolymorphisminautophagyrelatedgeneatg7modifiesageatonsetspecificallyinitalianhuntingtondiseasepatients AT jørgenenielsen v471apolymorphisminautophagyrelatedgeneatg7modifiesageatonsetspecificallyinitalianhuntingtondiseasepatients AT davidcraufurd v471apolymorphisminautophagyrelatedgeneatg7modifiesageatonsetspecificallyinitalianhuntingtondiseasepatients AT registryinvestigatorsoftheeuropeanhuntingtonsdiseasenetwork v471apolymorphisminautophagyrelatedgeneatg7modifiesageatonsetspecificallyinitalianhuntingtondiseasepatients AT huuphucnguyen v471apolymorphisminautophagyrelatedgeneatg7modifiesageatonsetspecificallyinitalianhuntingtondiseasepatients |