Comparison of the mutation spectrum and association with pre and post treatment lipid measures of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries

Detalhes bibliográficos
Autor(a) principal: Futema, Marta
Data de Publicação: 2021
Outros Autores: Ramaswami, Uma, Tichy, Lukas, Bogsrud, Martin P., Holven, Kirsten B., Roeters van Lennep, Jeanine, Wiegman, Albert, Descamps, Olivier S., De Leener, Anne, Fastre, Elodie, Vrablik, Michal, Freiberger, Tomas, Esterbauer, Harald, Dieplinger, Hans, Greber-Platzer, Susanne, Medeiros, Ana M., Bourbon, Mafalda, Mollaki, Vasiliki, Drogari, Euridiki, Humphries, Steve E.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/7993
Resumo: Background and aims: Familial hypercholesterolaemia (FH) is commonly caused by mutations in the LDLR, APOB or PCSK9 genes, with untreated mean low density lipoprotein-cholesterol (LDL-C) concentrations being elevated in APOB mutation carriers, even higher in LDLR mutation and highest in those with a PCSK9 mutation. Here we examine this in children with FH from Norway, UK, The Netherlands, Belgium, Czech Republic, Austria, Portugal and Greece. Methods: Differences in characteristics and pre- and post-treatment lipid concentrations in those with different molecular causes were compared by standard statistical tests. Results: Data were obtained from 2866 children, of whom 2531 (88%) carried a reported LDLR/APOB/PCSK9 variant. In all countries, the most common cause of FH was an LDLR mutation (79% of children, 297 different), but the prevalence of the APOB p.(Arg3527Gln) mutation varied significantly (ranging from 0% in Greece to 39% in Czech Republic, p < 2.2 × 10-16). The prevalence of a family history of premature CHD was significantly higher in children with an LDLR vs APOB mutation (16% vs 7% p=0.0005). Compared to the LDLR mutation group, mean (±SD) concentrations of pre-treatment LDL-C were significantly lower in those with an APOB mutation (n = 2260 vs n = 264, 4.96 (1.08)mmol/l vs 5.88 (1.41)mmol/l, p < 2.2 × 10-16) and lowest in those with a PCSK9 mutation (n = 7, 4.71 (1.22)mmol/l). Conclusions: The most common cause of FH in children from eight European countries was an LDLR mutation, with the prevalence of the APOB p.(Arg3527Gln) mutation varying significantly across countries. In children, LDLR-FH is associated with higher concentrations of LDL-C and family history of CHD compared to those with APOB-FH.
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spelling Comparison of the mutation spectrum and association with pre and post treatment lipid measures of children with heterozygous familial hypercholesterolaemia (FH) from eight European countriesHeterozygous Familial HypercholesterolaemiaMutation SpectrumLDL-C ConcentrationsStatin TreatmentEuropePortugalDoenças Cardio e Cérebro-vascularesBackground and aims: Familial hypercholesterolaemia (FH) is commonly caused by mutations in the LDLR, APOB or PCSK9 genes, with untreated mean low density lipoprotein-cholesterol (LDL-C) concentrations being elevated in APOB mutation carriers, even higher in LDLR mutation and highest in those with a PCSK9 mutation. Here we examine this in children with FH from Norway, UK, The Netherlands, Belgium, Czech Republic, Austria, Portugal and Greece. Methods: Differences in characteristics and pre- and post-treatment lipid concentrations in those with different molecular causes were compared by standard statistical tests. Results: Data were obtained from 2866 children, of whom 2531 (88%) carried a reported LDLR/APOB/PCSK9 variant. In all countries, the most common cause of FH was an LDLR mutation (79% of children, 297 different), but the prevalence of the APOB p.(Arg3527Gln) mutation varied significantly (ranging from 0% in Greece to 39% in Czech Republic, p < 2.2 × 10-16). The prevalence of a family history of premature CHD was significantly higher in children with an LDLR vs APOB mutation (16% vs 7% p=0.0005). Compared to the LDLR mutation group, mean (±SD) concentrations of pre-treatment LDL-C were significantly lower in those with an APOB mutation (n = 2260 vs n = 264, 4.96 (1.08)mmol/l vs 5.88 (1.41)mmol/l, p < 2.2 × 10-16) and lowest in those with a PCSK9 mutation (n = 7, 4.71 (1.22)mmol/l). Conclusions: The most common cause of FH in children from eight European countries was an LDLR mutation, with the prevalence of the APOB p.(Arg3527Gln) mutation varying significantly across countries. In children, LDLR-FH is associated with higher concentrations of LDL-C and family history of CHD compared to those with APOB-FH.Highlights: LDLR mutations are the most common cause of familial hypercholesterolaemia (FH) in children from 8 European countries; Overall, 279 different LDLR mutations were found in 2531 FH children; The frequency of APOB p.(Arg3527Gln) varied significantly over the 8 countries; APOB-FH was less severe than LDLR-FH for low density lipoprotein-cholesterol (LDL-C) concentration and family onset of coronary heart disease (CHD).The European Register is supported by a grant from the International Atherosclerosis Society (Pfizer number 24052829). The UK register is supported by funds from the British Heart Foundation (BHF); HEART UK, Cardiac Network Co-ordinating Group Wales and the Royal College of Physicians. SEH is a BHF Professor and is funded by PG08/008, and by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. MF is funded by the Fondation Leducq Transatlantic Networks of Excellence Program grant (no. 14 CVD03). MV is supported by the Ministry of Health, Czechia, project No. 64165, General University Hospital in Prague. TF and LT are supported by the Ministry of Health, Czechia, grant number NU20-02-00261. The Austrian FH register has been supported by funds from the Austrian Heart Foundation and the Tyrolean Regional Government. The Portuguese FH Study has been supported by grants from the Portuguese Science and Technology Foundation and grants from the Portuguese Cardiology Society. AMM was supported by the Portuguese Science and Technology Foundation, grant number SFRH/BD/113,017/2015. The study sponsors had no role in study design, the collection, analysis, and interpretation of data, the writing of the report or the decision to submit the manuscript for publication. No honorarium, grant, or other form of payment was given to anyone to produce the manuscript.Elsevier/European Atherosclerosis SocietyRepositório Científico do Instituto Nacional de SaúdeFutema, MartaRamaswami, UmaTichy, LukasBogsrud, Martin P.Holven, Kirsten B.Roeters van Lennep, JeanineWiegman, AlbertDescamps, Olivier S.De Leener, AnneFastre, ElodieVrablik, MichalFreiberger, TomasEsterbauer, HaraldDieplinger, HansGreber-Platzer, SusanneMedeiros, Ana M.Bourbon, MafaldaMollaki, VasilikiDrogari, EuridikiHumphries, Steve E.2022-03-23T17:14:39Z2021-01-122021-01-12T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/7993engAtherosclerosis. 2021 Feb;319:108-117. doi: 10.1016/j.atherosclerosis.2021.01.008. Epub 2021 Jan 13.0021-915010.1016/j.atherosclerosis.2021.01.008info:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:42:24Zoai:repositorio.insa.pt:10400.18/7993Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:42:47.275548Repositório 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 Comparison of the mutation spectrum and association with pre and post treatment lipid measures of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries
title Comparison of the mutation spectrum and association with pre and post treatment lipid measures of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries
spellingShingle Comparison of the mutation spectrum and association with pre and post treatment lipid measures of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries
Futema, Marta
Heterozygous Familial Hypercholesterolaemia
Mutation Spectrum
LDL-C Concentrations
Statin Treatment
Europe
Portugal
Doenças Cardio e Cérebro-vasculares
title_short Comparison of the mutation spectrum and association with pre and post treatment lipid measures of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries
title_full Comparison of the mutation spectrum and association with pre and post treatment lipid measures of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries
title_fullStr Comparison of the mutation spectrum and association with pre and post treatment lipid measures of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries
title_full_unstemmed Comparison of the mutation spectrum and association with pre and post treatment lipid measures of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries
title_sort Comparison of the mutation spectrum and association with pre and post treatment lipid measures of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries
author Futema, Marta
author_facet Futema, Marta
Ramaswami, Uma
Tichy, Lukas
Bogsrud, Martin P.
Holven, Kirsten B.
Roeters van Lennep, Jeanine
Wiegman, Albert
Descamps, Olivier S.
De Leener, Anne
Fastre, Elodie
Vrablik, Michal
Freiberger, Tomas
Esterbauer, Harald
Dieplinger, Hans
Greber-Platzer, Susanne
Medeiros, Ana M.
Bourbon, Mafalda
Mollaki, Vasiliki
Drogari, Euridiki
Humphries, Steve E.
author_role author
author2 Ramaswami, Uma
Tichy, Lukas
Bogsrud, Martin P.
Holven, Kirsten B.
Roeters van Lennep, Jeanine
Wiegman, Albert
Descamps, Olivier S.
De Leener, Anne
Fastre, Elodie
Vrablik, Michal
Freiberger, Tomas
Esterbauer, Harald
Dieplinger, Hans
Greber-Platzer, Susanne
Medeiros, Ana M.
Bourbon, Mafalda
Mollaki, Vasiliki
Drogari, Euridiki
Humphries, Steve E.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
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 Futema, Marta
Ramaswami, Uma
Tichy, Lukas
Bogsrud, Martin P.
Holven, Kirsten B.
Roeters van Lennep, Jeanine
Wiegman, Albert
Descamps, Olivier S.
De Leener, Anne
Fastre, Elodie
Vrablik, Michal
Freiberger, Tomas
Esterbauer, Harald
Dieplinger, Hans
Greber-Platzer, Susanne
Medeiros, Ana M.
Bourbon, Mafalda
Mollaki, Vasiliki
Drogari, Euridiki
Humphries, Steve E.
dc.subject.por.fl_str_mv Heterozygous Familial Hypercholesterolaemia
Mutation Spectrum
LDL-C Concentrations
Statin Treatment
Europe
Portugal
Doenças Cardio e Cérebro-vasculares
topic Heterozygous Familial Hypercholesterolaemia
Mutation Spectrum
LDL-C Concentrations
Statin Treatment
Europe
Portugal
Doenças Cardio e Cérebro-vasculares
description Background and aims: Familial hypercholesterolaemia (FH) is commonly caused by mutations in the LDLR, APOB or PCSK9 genes, with untreated mean low density lipoprotein-cholesterol (LDL-C) concentrations being elevated in APOB mutation carriers, even higher in LDLR mutation and highest in those with a PCSK9 mutation. Here we examine this in children with FH from Norway, UK, The Netherlands, Belgium, Czech Republic, Austria, Portugal and Greece. Methods: Differences in characteristics and pre- and post-treatment lipid concentrations in those with different molecular causes were compared by standard statistical tests. Results: Data were obtained from 2866 children, of whom 2531 (88%) carried a reported LDLR/APOB/PCSK9 variant. In all countries, the most common cause of FH was an LDLR mutation (79% of children, 297 different), but the prevalence of the APOB p.(Arg3527Gln) mutation varied significantly (ranging from 0% in Greece to 39% in Czech Republic, p < 2.2 × 10-16). The prevalence of a family history of premature CHD was significantly higher in children with an LDLR vs APOB mutation (16% vs 7% p=0.0005). Compared to the LDLR mutation group, mean (±SD) concentrations of pre-treatment LDL-C were significantly lower in those with an APOB mutation (n = 2260 vs n = 264, 4.96 (1.08)mmol/l vs 5.88 (1.41)mmol/l, p < 2.2 × 10-16) and lowest in those with a PCSK9 mutation (n = 7, 4.71 (1.22)mmol/l). Conclusions: The most common cause of FH in children from eight European countries was an LDLR mutation, with the prevalence of the APOB p.(Arg3527Gln) mutation varying significantly across countries. In children, LDLR-FH is associated with higher concentrations of LDL-C and family history of CHD compared to those with APOB-FH.
publishDate 2021
dc.date.none.fl_str_mv 2021-01-12
2021-01-12T00:00:00Z
2022-03-23T17:14:39Z
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/10400.18/7993
url http://hdl.handle.net/10400.18/7993
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Atherosclerosis. 2021 Feb;319:108-117. doi: 10.1016/j.atherosclerosis.2021.01.008. Epub 2021 Jan 13.
0021-9150
10.1016/j.atherosclerosis.2021.01.008
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
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dc.publisher.none.fl_str_mv Elsevier/European Atherosclerosis Society
publisher.none.fl_str_mv Elsevier/European Atherosclerosis Society
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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