Intermediate Repeat Expansion in the ATXN2 Gene as a Risk Factor in the ALS and FTD Spanish Population
Intermediate CAG expansions in the gene ataxin-2 (ATXN2) are a known risk factor for ALS, but little is known about their role in FTD risk. Moreover, their contribution to the risk and phenotype of patients might vary in populations with different genetic backgrounds. The aim of this study was to as...
| Autores: | , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/209702 |
| Acceso en línea: | https://hdl.handle.net/2445/209702 |
| Access Level: | acceso abierto |
| Palabra clave: | Esclerosi lateral amiotròfica Genètica mèdica Amyotrophic lateral sclerosis Medical genetics |
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Intermediate Repeat Expansion in the ATXN2 Gene as a Risk Factor in the ALS and FTD Spanish PopulationBorrego Hernández, DanielVázquez Costa, Juan FranciscoDomínguez Rubio, RaúlExpósito Blázquez, LauraAller, ElenaPadró Miquel, AriadnaGarcía Casanova, PilarColomina, María J.Martín Arriscado, CristinaOsta, RosarioCordero Vázquez, PilarEsteban Pérez, JesúsPovedano Panadés, MónicaGarcía Redondo, AlbertoEsclerosi lateral amiotròficaGenètica mèdicaAmyotrophic lateral sclerosisMedical geneticsIntermediate CAG expansions in the gene ataxin-2 (ATXN2) are a known risk factor for ALS, but little is known about their role in FTD risk. Moreover, their contribution to the risk and phenotype of patients might vary in populations with different genetic backgrounds. The aim of this study was to assess the relationship of intermediate CAG expansions in ATXN2 with the risk and phenotype of ALS and FTD in the Spanish population. Repeat-primed PCR was performed in 620 ALS and 137 FTD patients in three referral centers in Spain to determine the exact number of CAG repeats. In our cohort, >= 27 CAG repeats in ATXN2 were associated with a higher risk of developing ALS (odds ratio [OR] = 2.666 [1.471-4.882]; p = 0.0013) but not FTD (odds ratio [OR] = 1.446 [0.558-3.574]; p = 0.44). Moreover, ALS patients with >= 27 CAG repeats in ATXN2 showed a shorter survival rate compared to those with <27 repeats (hazard ratio [HR] 1.74 [1.18, 2.56], p = 0.005), more frequent limb onset (odds ratio [OR] = 2.34 [1.093-4.936]; p = 0.028) and a family history of ALS (odds ratio [OR] = 2.538 [1.375-4.634]; p = 0.002). Intermediate CAG expansions of >= 27 repeats in ATXN2 are associated with ALS risk but not with FTD in the Spanish population. ALS patients carrying an intermediate expansion in ATXN2 show more frequent limb onset but a worse prognosis than those without expansions. In patients carrying C9orf72 expansions, the intermediate ATXN2 expansion might increase the penetrance and modify the phenotype.MDPI AG2024202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfhttps://hdl.handle.net/2445/209702Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/biomedicines12020356Biomedicines, 2024, vol. 12, num. 2https://doi.org/10.3390/biomedicines12020356cc by (c) Borrego Hernández, Daniel et al, 2024http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2097022026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Intermediate Repeat Expansion in the ATXN2 Gene as a Risk Factor in the ALS and FTD Spanish Population |
| title |
Intermediate Repeat Expansion in the ATXN2 Gene as a Risk Factor in the ALS and FTD Spanish Population |
| spellingShingle |
Intermediate Repeat Expansion in the ATXN2 Gene as a Risk Factor in the ALS and FTD Spanish Population Borrego Hernández, Daniel Esclerosi lateral amiotròfica Genètica mèdica Amyotrophic lateral sclerosis Medical genetics |
| title_short |
Intermediate Repeat Expansion in the ATXN2 Gene as a Risk Factor in the ALS and FTD Spanish Population |
| title_full |
Intermediate Repeat Expansion in the ATXN2 Gene as a Risk Factor in the ALS and FTD Spanish Population |
| title_fullStr |
Intermediate Repeat Expansion in the ATXN2 Gene as a Risk Factor in the ALS and FTD Spanish Population |
| title_full_unstemmed |
Intermediate Repeat Expansion in the ATXN2 Gene as a Risk Factor in the ALS and FTD Spanish Population |
| title_sort |
Intermediate Repeat Expansion in the ATXN2 Gene as a Risk Factor in the ALS and FTD Spanish Population |
| dc.creator.none.fl_str_mv |
Borrego Hernández, Daniel Vázquez Costa, Juan Francisco Domínguez Rubio, Raúl Expósito Blázquez, Laura Aller, Elena Padró Miquel, Ariadna García Casanova, Pilar Colomina, María J. Martín Arriscado, Cristina Osta, Rosario Cordero Vázquez, Pilar Esteban Pérez, Jesús Povedano Panadés, Mónica García Redondo, Alberto |
| author |
Borrego Hernández, Daniel |
| author_facet |
Borrego Hernández, Daniel Vázquez Costa, Juan Francisco Domínguez Rubio, Raúl Expósito Blázquez, Laura Aller, Elena Padró Miquel, Ariadna García Casanova, Pilar Colomina, María J. Martín Arriscado, Cristina Osta, Rosario Cordero Vázquez, Pilar Esteban Pérez, Jesús Povedano Panadés, Mónica García Redondo, Alberto |
| author_role |
author |
| author2 |
Vázquez Costa, Juan Francisco Domínguez Rubio, Raúl Expósito Blázquez, Laura Aller, Elena Padró Miquel, Ariadna García Casanova, Pilar Colomina, María J. Martín Arriscado, Cristina Osta, Rosario Cordero Vázquez, Pilar Esteban Pérez, Jesús Povedano Panadés, Mónica García Redondo, Alberto |
| author2_role |
author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Esclerosi lateral amiotròfica Genètica mèdica Amyotrophic lateral sclerosis Medical genetics |
| topic |
Esclerosi lateral amiotròfica Genètica mèdica Amyotrophic lateral sclerosis Medical genetics |
| description |
Intermediate CAG expansions in the gene ataxin-2 (ATXN2) are a known risk factor for ALS, but little is known about their role in FTD risk. Moreover, their contribution to the risk and phenotype of patients might vary in populations with different genetic backgrounds. The aim of this study was to assess the relationship of intermediate CAG expansions in ATXN2 with the risk and phenotype of ALS and FTD in the Spanish population. Repeat-primed PCR was performed in 620 ALS and 137 FTD patients in three referral centers in Spain to determine the exact number of CAG repeats. In our cohort, >= 27 CAG repeats in ATXN2 were associated with a higher risk of developing ALS (odds ratio [OR] = 2.666 [1.471-4.882]; p = 0.0013) but not FTD (odds ratio [OR] = 1.446 [0.558-3.574]; p = 0.44). Moreover, ALS patients with >= 27 CAG repeats in ATXN2 showed a shorter survival rate compared to those with <27 repeats (hazard ratio [HR] 1.74 [1.18, 2.56], p = 0.005), more frequent limb onset (odds ratio [OR] = 2.34 [1.093-4.936]; p = 0.028) and a family history of ALS (odds ratio [OR] = 2.538 [1.375-4.634]; p = 0.002). Intermediate CAG expansions of >= 27 repeats in ATXN2 are associated with ALS risk but not with FTD in the Spanish population. ALS patients carrying an intermediate expansion in ATXN2 show more frequent limb onset but a worse prognosis than those without expansions. In patients carrying C9orf72 expansions, the intermediate ATXN2 expansion might increase the penetrance and modify the phenotype. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2024 2024 2024 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/209702 |
| url |
https://hdl.handle.net/2445/209702 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.3390/biomedicines12020356 Biomedicines, 2024, vol. 12, num. 2 https://doi.org/10.3390/biomedicines12020356 |
| dc.rights.none.fl_str_mv |
cc by (c) Borrego Hernández, Daniel et al, 2024 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc by (c) Borrego Hernández, Daniel et al, 2024 http://creativecommons.org/licenses/by/3.0/es/ |
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openAccess |
| dc.format.none.fl_str_mv |
13 p. application/pdf |
| dc.publisher.none.fl_str_mv |
MDPI AG |
| publisher.none.fl_str_mv |
MDPI AG |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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