The familial hypercholesterolaemia phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causes
Autor(a) principal: | |
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Data de Publicação: | 2019 |
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/10400.18/6563 |
Resumo: | Familial Hypercholesterolaemia (FH) is a monogenic disorder characterised by high LDL-C concentrations and increased cardiovascular risk. However, in clinically defined FH cohorts worldwide, an FH-causing variant is only found in 40-50% of the cases. The aim of this work was to characterise the genetic cause of the FH phenotype in Portuguese clinical FH patients. Methods and Results Between 1999 and 2017, 731 index patients (311 children and 420 adults) who met the Simon Broome diagnostic criteria had been referred to our laboratory. LDLR, APOB, PCSK9, APOE, LIPA, LDLRAP1, ABCG5/8 genes were analysed by PCR amplification and Sanger sequencing. The 6-SNP LDL-C genetic risk score (GRS) for polygenic hypercholesterolaemia was validated in the Portuguese population and cases with a GRS over the 25th percentile were considered to have a high likelihood of polygenic hypercholesterolaemia. An FH-causing mutation was found in 39% of patients (94% in LDLR, 5% APOB and 1% PCSK9), while at least 29% have polygenic hypercholesterolaemia and 1% have other lipid disorders. A genetic cause for the FH phenotype was found in 503 patients (69%). All known causes of the FH phenotype should be investigated in FH cohorts to ensure accurate diagnosis and appropriate management. |
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The familial hypercholesterolaemia phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causesThe FH phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causesFH phenotype: monogenic, polygenic and other causesFamilial HypercholesterolaemiaGenetic Risk ScoreMonogenic DyslipidaemiaPhenocopiesPolygenic HypercholesterolaemiaHipercolesterolemia FamiliarDoenças Cardio e Cérebro-vascularesFamilial Hypercholesterolaemia (FH) is a monogenic disorder characterised by high LDL-C concentrations and increased cardiovascular risk. However, in clinically defined FH cohorts worldwide, an FH-causing variant is only found in 40-50% of the cases. The aim of this work was to characterise the genetic cause of the FH phenotype in Portuguese clinical FH patients. Methods and Results Between 1999 and 2017, 731 index patients (311 children and 420 adults) who met the Simon Broome diagnostic criteria had been referred to our laboratory. LDLR, APOB, PCSK9, APOE, LIPA, LDLRAP1, ABCG5/8 genes were analysed by PCR amplification and Sanger sequencing. The 6-SNP LDL-C genetic risk score (GRS) for polygenic hypercholesterolaemia was validated in the Portuguese population and cases with a GRS over the 25th percentile were considered to have a high likelihood of polygenic hypercholesterolaemia. An FH-causing mutation was found in 39% of patients (94% in LDLR, 5% APOB and 1% PCSK9), while at least 29% have polygenic hypercholesterolaemia and 1% have other lipid disorders. A genetic cause for the FH phenotype was found in 503 patients (69%). All known causes of the FH phenotype should be investigated in FH cohorts to ensure accurate diagnosis and appropriate management.Cibelle Mariano was supported by a PhD student grant [SFRH/BD/52494/2014]. Marta Futema is supported by the Fondation Leducq Transatlantic Networks of Excellence Program grant (no 14 CVD03). The work of Marilia Antunes is partially funded by UID/MAT/000016/2019. SEH acknowledges funding from the British Heart Foundation grant (BHF PG08/008) and from the NIHR UCLH BRC. MB acknowledges funding from Science and Technology Foundation (PIC/IC/83020/2007) (PIC/IC/83333/2007) for the e_COR and Portuguese FH Study and from Portuguese Cardiology Society for the Portuguese FH Study.John Wiley and SonsRepositório Científico do Instituto Nacional de SaúdeMariano, C.Alves, A.C.Medeiros, A.Chora, J.R.Antunes, M.Futema, M.Humphries, S.E.Bourbon, M.2020-04-30T20:55:10Z2019-12-192019-12-19T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/10400.18/6563engClin Genet. 2020 Mar;97(3):457-466. doi: 10.1111/cge.13697. Epub 2019 Dec 310009-916310.1111/cge.13697info: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:RCAAP2023-07-20T15:41:36Zoai:repositorio.insa.pt:10400.18/6563Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:41:24.520434Repositório 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 |
The familial hypercholesterolaemia phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causes The FH phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causes FH phenotype: monogenic, polygenic and other causes |
title |
The familial hypercholesterolaemia phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causes |
spellingShingle |
The familial hypercholesterolaemia phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causes Mariano, C. Familial Hypercholesterolaemia Genetic Risk Score Monogenic Dyslipidaemia Phenocopies Polygenic Hypercholesterolaemia Hipercolesterolemia Familiar Doenças Cardio e Cérebro-vasculares |
title_short |
The familial hypercholesterolaemia phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causes |
title_full |
The familial hypercholesterolaemia phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causes |
title_fullStr |
The familial hypercholesterolaemia phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causes |
title_full_unstemmed |
The familial hypercholesterolaemia phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causes |
title_sort |
The familial hypercholesterolaemia phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causes |
author |
Mariano, C. |
author_facet |
Mariano, C. Alves, A.C. Medeiros, A. Chora, J.R. Antunes, M. Futema, M. Humphries, S.E. Bourbon, M. |
author_role |
author |
author2 |
Alves, A.C. Medeiros, A. Chora, J.R. Antunes, M. Futema, M. Humphries, S.E. Bourbon, M. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Mariano, C. Alves, A.C. Medeiros, A. Chora, J.R. Antunes, M. Futema, M. Humphries, S.E. Bourbon, M. |
dc.subject.por.fl_str_mv |
Familial Hypercholesterolaemia Genetic Risk Score Monogenic Dyslipidaemia Phenocopies Polygenic Hypercholesterolaemia Hipercolesterolemia Familiar Doenças Cardio e Cérebro-vasculares |
topic |
Familial Hypercholesterolaemia Genetic Risk Score Monogenic Dyslipidaemia Phenocopies Polygenic Hypercholesterolaemia Hipercolesterolemia Familiar Doenças Cardio e Cérebro-vasculares |
description |
Familial Hypercholesterolaemia (FH) is a monogenic disorder characterised by high LDL-C concentrations and increased cardiovascular risk. However, in clinically defined FH cohorts worldwide, an FH-causing variant is only found in 40-50% of the cases. The aim of this work was to characterise the genetic cause of the FH phenotype in Portuguese clinical FH patients. Methods and Results Between 1999 and 2017, 731 index patients (311 children and 420 adults) who met the Simon Broome diagnostic criteria had been referred to our laboratory. LDLR, APOB, PCSK9, APOE, LIPA, LDLRAP1, ABCG5/8 genes were analysed by PCR amplification and Sanger sequencing. The 6-SNP LDL-C genetic risk score (GRS) for polygenic hypercholesterolaemia was validated in the Portuguese population and cases with a GRS over the 25th percentile were considered to have a high likelihood of polygenic hypercholesterolaemia. An FH-causing mutation was found in 39% of patients (94% in LDLR, 5% APOB and 1% PCSK9), while at least 29% have polygenic hypercholesterolaemia and 1% have other lipid disorders. A genetic cause for the FH phenotype was found in 503 patients (69%). All known causes of the FH phenotype should be investigated in FH cohorts to ensure accurate diagnosis and appropriate management. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-12-19 2019-12-19T00:00:00Z 2020-04-30T20:55:10Z |
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/10400.18/6563 |
url |
http://hdl.handle.net/10400.18/6563 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Clin Genet. 2020 Mar;97(3):457-466. doi: 10.1111/cge.13697. Epub 2019 Dec 31 0009-9163 10.1111/cge.13697 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
John Wiley and Sons |
publisher.none.fl_str_mv |
John Wiley and Sons |
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 |
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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) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132158158176256 |