Familial amyloid polyneuropathy in Portugal: New genes modulating age-at-onset
Autor(a) principal: | |
---|---|
Data de Publicação: | 2017 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.16/2075 |
Resumo: | OBJECTIVES: Familial amyloid polyneuropathy (FAP ATTRV30M) shows a wide variation in age-at-onset (AO) between clusters, families, and among generations. We will now explore some candidate genes involved in altered disease pathways in order to assess their role as genetic modifiers of AO, using a family-centered approach. METHODS: We analyzed 62 tagging SNPs from nine genes-NGAL,MMP-9,BGN,MEK1,MEK2,ERK1,ERK2,HSP27, and YWHAZ - in a sample of 318 V30M Portuguese patients (106 families), currently under follow-up. A generalized estimating equation analysis was used to take into account nonindependency of AO between relatives. Also, an in silico analysis was performed in order to assess the functional impact of significant variants associated with AO. RESULTS: We found for the first time variants from six genes (NGAL,BGN (in the female group), MEK1,MEK2,HSP27, and YWHAZ) that were significantly associated with early- and/or late-onset. Then, we confirmed a strong synergistic interaction between NGAL and MMP-9 genes. Additionally, by an in silico analysis, we found some variants for MEK1 gene that may alter binding of the transcription factors and that influence the regulation of gene expression regarding microRNA binding sites and splicing regulatory factors. INTERPRETATION: These findings showed that different genetic factors can modulate differently the onset of disease's symptoms and revealed new mechanisms with clinical implications in the genetic counseling and follow-up of mutation carriers and could contribute for development of potential therapeutical targets. |
id |
RCAP_f03501e7323aafd65cac932eb7732b9f |
---|---|
oai_identifier_str |
oai:repositorio.chporto.pt:10400.16/2075 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Familial amyloid polyneuropathy in Portugal: New genes modulating age-at-onsetOBJECTIVES: Familial amyloid polyneuropathy (FAP ATTRV30M) shows a wide variation in age-at-onset (AO) between clusters, families, and among generations. We will now explore some candidate genes involved in altered disease pathways in order to assess their role as genetic modifiers of AO, using a family-centered approach. METHODS: We analyzed 62 tagging SNPs from nine genes-NGAL,MMP-9,BGN,MEK1,MEK2,ERK1,ERK2,HSP27, and YWHAZ - in a sample of 318 V30M Portuguese patients (106 families), currently under follow-up. A generalized estimating equation analysis was used to take into account nonindependency of AO between relatives. Also, an in silico analysis was performed in order to assess the functional impact of significant variants associated with AO. RESULTS: We found for the first time variants from six genes (NGAL,BGN (in the female group), MEK1,MEK2,HSP27, and YWHAZ) that were significantly associated with early- and/or late-onset. Then, we confirmed a strong synergistic interaction between NGAL and MMP-9 genes. Additionally, by an in silico analysis, we found some variants for MEK1 gene that may alter binding of the transcription factors and that influence the regulation of gene expression regarding microRNA binding sites and splicing regulatory factors. INTERPRETATION: These findings showed that different genetic factors can modulate differently the onset of disease's symptoms and revealed new mechanisms with clinical implications in the genetic counseling and follow-up of mutation carriers and could contribute for development of potential therapeutical targets.American Neurological AssociationRepositório Científico do Centro Hospitalar Universitário de Santo AntónioSantos, D.Coelho, T.Alves-Ferreira, M.Sequeiros, J.Mendonça, D.Alonso, I.Lemos, C.Sousa, A.2017-04-24T14:30:26Z20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.16/2075engAnn Clin Transl Neurol. 2017 20;4(2):98-1052328-950310.1002/acn3.380info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-20T10:59:00Zoai:repositorio.chporto.pt:10400.16/2075Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:38:21.213932Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Familial amyloid polyneuropathy in Portugal: New genes modulating age-at-onset |
title |
Familial amyloid polyneuropathy in Portugal: New genes modulating age-at-onset |
spellingShingle |
Familial amyloid polyneuropathy in Portugal: New genes modulating age-at-onset Santos, D. |
title_short |
Familial amyloid polyneuropathy in Portugal: New genes modulating age-at-onset |
title_full |
Familial amyloid polyneuropathy in Portugal: New genes modulating age-at-onset |
title_fullStr |
Familial amyloid polyneuropathy in Portugal: New genes modulating age-at-onset |
title_full_unstemmed |
Familial amyloid polyneuropathy in Portugal: New genes modulating age-at-onset |
title_sort |
Familial amyloid polyneuropathy in Portugal: New genes modulating age-at-onset |
author |
Santos, D. |
author_facet |
Santos, D. Coelho, T. Alves-Ferreira, M. Sequeiros, J. Mendonça, D. Alonso, I. Lemos, C. Sousa, A. |
author_role |
author |
author2 |
Coelho, T. Alves-Ferreira, M. Sequeiros, J. Mendonça, D. Alonso, I. Lemos, C. Sousa, A. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Centro Hospitalar Universitário de Santo António |
dc.contributor.author.fl_str_mv |
Santos, D. Coelho, T. Alves-Ferreira, M. Sequeiros, J. Mendonça, D. Alonso, I. Lemos, C. Sousa, A. |
description |
OBJECTIVES: Familial amyloid polyneuropathy (FAP ATTRV30M) shows a wide variation in age-at-onset (AO) between clusters, families, and among generations. We will now explore some candidate genes involved in altered disease pathways in order to assess their role as genetic modifiers of AO, using a family-centered approach. METHODS: We analyzed 62 tagging SNPs from nine genes-NGAL,MMP-9,BGN,MEK1,MEK2,ERK1,ERK2,HSP27, and YWHAZ - in a sample of 318 V30M Portuguese patients (106 families), currently under follow-up. A generalized estimating equation analysis was used to take into account nonindependency of AO between relatives. Also, an in silico analysis was performed in order to assess the functional impact of significant variants associated with AO. RESULTS: We found for the first time variants from six genes (NGAL,BGN (in the female group), MEK1,MEK2,HSP27, and YWHAZ) that were significantly associated with early- and/or late-onset. Then, we confirmed a strong synergistic interaction between NGAL and MMP-9 genes. Additionally, by an in silico analysis, we found some variants for MEK1 gene that may alter binding of the transcription factors and that influence the regulation of gene expression regarding microRNA binding sites and splicing regulatory factors. INTERPRETATION: These findings showed that different genetic factors can modulate differently the onset of disease's symptoms and revealed new mechanisms with clinical implications in the genetic counseling and follow-up of mutation carriers and could contribute for development of potential therapeutical targets. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-04-24T14:30:26Z 2017 2017-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.16/2075 |
url |
http://hdl.handle.net/10400.16/2075 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Ann Clin Transl Neurol. 2017 20;4(2):98-105 2328-9503 10.1002/acn3.380 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
American Neurological Association |
publisher.none.fl_str_mv |
American Neurological Association |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799133644952961024 |