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Implementation of a biochemical, clinical, and genetic screening programme for familial hypercholesterolemia in 26 centres in Spain: The ARIAN study

Background: Familial hypercholesterolemia (FH) is clearly underdiagnosed and undertreated. The aim of this present study is to assess the benefits of FH screening through a joint national program implemented between clinical laboratories and lipid units. Methods: All clinical laboratory tests from 1...

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Autores principales: Arrobas Velilla, Teresa, Brea, Ángel, Valdivielso, Pedro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465084/
https://www.ncbi.nlm.nih.gov/pubmed/36105085
http://dx.doi.org/10.3389/fgene.2022.971651
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author Arrobas Velilla, Teresa
Brea, Ángel
Valdivielso, Pedro
author_facet Arrobas Velilla, Teresa
Brea, Ángel
Valdivielso, Pedro
author_sort Arrobas Velilla, Teresa
collection PubMed
description Background: Familial hypercholesterolemia (FH) is clearly underdiagnosed and undertreated. The aim of this present study is to assess the benefits of FH screening through a joint national program implemented between clinical laboratories and lipid units. Methods: All clinical laboratory tests from 1 January 2017 to 31 December 2018 were reviewed, and those with LDL cholesterol (LDL-C) levels >250 mg/dl were identified in subjects >18 years of age of both sexes. Once secondary causes had been ruled out, the treating physician was contacted and advised to refer the patient to an LU to perform the Dutch Lipid Clinic Network score and to request genetic testing if the score was ≥6 points. Next Generation Sequencing was used to analyse the promoter and coding DNA sequences of four genes associated with FH (LDLR, APOB, PCSK9, APOE) and two genes that have a clinical overlap with FH characteristics (LDLRAP1 and LIPA). A polygenic risk score based on 12 variants was also obtained. Results: Of the 3,827,513 patients analyzed in 26 centers, 6,765 had LDL-C levels >250 mg/dl. Having ruled out secondary causes and known cases of FH, 3,015 subjects were included, although only 1,205 treating physicians could be contacted. 635 patients were referred to an LU and genetic testing was requested for 153 of them. This resulted in a finding of sixty-seven pathogenic variants for FH, 66 in the LDLR gene and one in APOB. The polygenic risk score was found higher in those who had no pathogenic variant compared to those with a pathogenic variant. Conclusion: Despite its limitations, systematic collaboration between clinical laboratories and lipid units allows for the identification of large numbers of patients with a phenotypic or genetic diagnosis of FH, which will reduce their vascular risk. This activity should be part of the clinical routine.
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spelling pubmed-94650842022-09-13 Implementation of a biochemical, clinical, and genetic screening programme for familial hypercholesterolemia in 26 centres in Spain: The ARIAN study Arrobas Velilla, Teresa Brea, Ángel Valdivielso, Pedro Front Genet Genetics Background: Familial hypercholesterolemia (FH) is clearly underdiagnosed and undertreated. The aim of this present study is to assess the benefits of FH screening through a joint national program implemented between clinical laboratories and lipid units. Methods: All clinical laboratory tests from 1 January 2017 to 31 December 2018 were reviewed, and those with LDL cholesterol (LDL-C) levels >250 mg/dl were identified in subjects >18 years of age of both sexes. Once secondary causes had been ruled out, the treating physician was contacted and advised to refer the patient to an LU to perform the Dutch Lipid Clinic Network score and to request genetic testing if the score was ≥6 points. Next Generation Sequencing was used to analyse the promoter and coding DNA sequences of four genes associated with FH (LDLR, APOB, PCSK9, APOE) and two genes that have a clinical overlap with FH characteristics (LDLRAP1 and LIPA). A polygenic risk score based on 12 variants was also obtained. Results: Of the 3,827,513 patients analyzed in 26 centers, 6,765 had LDL-C levels >250 mg/dl. Having ruled out secondary causes and known cases of FH, 3,015 subjects were included, although only 1,205 treating physicians could be contacted. 635 patients were referred to an LU and genetic testing was requested for 153 of them. This resulted in a finding of sixty-seven pathogenic variants for FH, 66 in the LDLR gene and one in APOB. The polygenic risk score was found higher in those who had no pathogenic variant compared to those with a pathogenic variant. Conclusion: Despite its limitations, systematic collaboration between clinical laboratories and lipid units allows for the identification of large numbers of patients with a phenotypic or genetic diagnosis of FH, which will reduce their vascular risk. This activity should be part of the clinical routine. Frontiers Media S.A. 2022-08-29 /pmc/articles/PMC9465084/ /pubmed/36105085 http://dx.doi.org/10.3389/fgene.2022.971651 Text en Copyright © 2022 Arrobas Velilla, Brea and Valdivielso. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Arrobas Velilla, Teresa
Brea, Ángel
Valdivielso, Pedro
Implementation of a biochemical, clinical, and genetic screening programme for familial hypercholesterolemia in 26 centres in Spain: The ARIAN study
title Implementation of a biochemical, clinical, and genetic screening programme for familial hypercholesterolemia in 26 centres in Spain: The ARIAN study
title_full Implementation of a biochemical, clinical, and genetic screening programme for familial hypercholesterolemia in 26 centres in Spain: The ARIAN study
title_fullStr Implementation of a biochemical, clinical, and genetic screening programme for familial hypercholesterolemia in 26 centres in Spain: The ARIAN study
title_full_unstemmed Implementation of a biochemical, clinical, and genetic screening programme for familial hypercholesterolemia in 26 centres in Spain: The ARIAN study
title_short Implementation of a biochemical, clinical, and genetic screening programme for familial hypercholesterolemia in 26 centres in Spain: The ARIAN study
title_sort implementation of a biochemical, clinical, and genetic screening programme for familial hypercholesterolemia in 26 centres in spain: the arian study
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465084/
https://www.ncbi.nlm.nih.gov/pubmed/36105085
http://dx.doi.org/10.3389/fgene.2022.971651
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