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Molecular Genetic Approach and Evaluation of Cardiovascular Events in Patients with Clinical Familial Hypercholesterolemia Phenotype from Romania

This study identifies the genetic background of familial hypercholesterolemia (FH) patients in Romania and evaluates the association between mutations and cardiovascular events. We performed a prospective observational study of 61 patients with a clinical diagnosis of FH selected based on Dutch Lipi...

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Autores principales: Vlad, Cristiana-Elena, Foia, Liliana Georgeta, Popescu, Roxana, Popa, Ioana, Aanicai, Ruxandra, Reurean-Pintilei, Delia, Toma, Vasilica, Florea, Laura, Kanbay, Mehmet, Covic, Adrian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036385/
https://www.ncbi.nlm.nih.gov/pubmed/33807407
http://dx.doi.org/10.3390/jcm10071399
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author Vlad, Cristiana-Elena
Foia, Liliana Georgeta
Popescu, Roxana
Popa, Ioana
Aanicai, Ruxandra
Reurean-Pintilei, Delia
Toma, Vasilica
Florea, Laura
Kanbay, Mehmet
Covic, Adrian
author_facet Vlad, Cristiana-Elena
Foia, Liliana Georgeta
Popescu, Roxana
Popa, Ioana
Aanicai, Ruxandra
Reurean-Pintilei, Delia
Toma, Vasilica
Florea, Laura
Kanbay, Mehmet
Covic, Adrian
author_sort Vlad, Cristiana-Elena
collection PubMed
description This study identifies the genetic background of familial hypercholesterolemia (FH) patients in Romania and evaluates the association between mutations and cardiovascular events. We performed a prospective observational study of 61 patients with a clinical diagnosis of FH selected based on Dutch Lipid Clinic Network (DLCN) and Simon Broome score between 2017 and 2020. Two techniques were used to identify mutations: multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. The mutation rate was 37.7%, i.e., 23 patients with mutations were identified, of which 7 subjects had pathogenic mutations and 16 had polymorphisms. Moreover, 10 variants of the low-density lipoprotein receptor (LDLR) gene were identified in 22 patients, i.e., one variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene in six patients, and one variant of the apolipoprotein B (APOB) gene in three patients. Of the LDLR gene variants, four were LDLR pathogenic mutations (c.81C > G, c.502G > A, c.1618G > A mutations in exon 2, exon 4, exon 11, and exon 13–15 duplication). The PCSK9 and APOB gene variants were benign mutations. The pathogenic LDLR mutations were significant predictors of the new cardiovascular events, and the time interval for new cardiovascular events occurrence was significantly decreased, compared to FH patients without mutations. In total, 12 variants were identified, with four pathogenic variants identified in the LDLR gene, whereas 62.3% of the study population displayed no pathological mutations.
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spelling pubmed-80363852021-04-12 Molecular Genetic Approach and Evaluation of Cardiovascular Events in Patients with Clinical Familial Hypercholesterolemia Phenotype from Romania Vlad, Cristiana-Elena Foia, Liliana Georgeta Popescu, Roxana Popa, Ioana Aanicai, Ruxandra Reurean-Pintilei, Delia Toma, Vasilica Florea, Laura Kanbay, Mehmet Covic, Adrian J Clin Med Article This study identifies the genetic background of familial hypercholesterolemia (FH) patients in Romania and evaluates the association between mutations and cardiovascular events. We performed a prospective observational study of 61 patients with a clinical diagnosis of FH selected based on Dutch Lipid Clinic Network (DLCN) and Simon Broome score between 2017 and 2020. Two techniques were used to identify mutations: multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. The mutation rate was 37.7%, i.e., 23 patients with mutations were identified, of which 7 subjects had pathogenic mutations and 16 had polymorphisms. Moreover, 10 variants of the low-density lipoprotein receptor (LDLR) gene were identified in 22 patients, i.e., one variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene in six patients, and one variant of the apolipoprotein B (APOB) gene in three patients. Of the LDLR gene variants, four were LDLR pathogenic mutations (c.81C > G, c.502G > A, c.1618G > A mutations in exon 2, exon 4, exon 11, and exon 13–15 duplication). The PCSK9 and APOB gene variants were benign mutations. The pathogenic LDLR mutations were significant predictors of the new cardiovascular events, and the time interval for new cardiovascular events occurrence was significantly decreased, compared to FH patients without mutations. In total, 12 variants were identified, with four pathogenic variants identified in the LDLR gene, whereas 62.3% of the study population displayed no pathological mutations. MDPI 2021-03-31 /pmc/articles/PMC8036385/ /pubmed/33807407 http://dx.doi.org/10.3390/jcm10071399 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vlad, Cristiana-Elena
Foia, Liliana Georgeta
Popescu, Roxana
Popa, Ioana
Aanicai, Ruxandra
Reurean-Pintilei, Delia
Toma, Vasilica
Florea, Laura
Kanbay, Mehmet
Covic, Adrian
Molecular Genetic Approach and Evaluation of Cardiovascular Events in Patients with Clinical Familial Hypercholesterolemia Phenotype from Romania
title Molecular Genetic Approach and Evaluation of Cardiovascular Events in Patients with Clinical Familial Hypercholesterolemia Phenotype from Romania
title_full Molecular Genetic Approach and Evaluation of Cardiovascular Events in Patients with Clinical Familial Hypercholesterolemia Phenotype from Romania
title_fullStr Molecular Genetic Approach and Evaluation of Cardiovascular Events in Patients with Clinical Familial Hypercholesterolemia Phenotype from Romania
title_full_unstemmed Molecular Genetic Approach and Evaluation of Cardiovascular Events in Patients with Clinical Familial Hypercholesterolemia Phenotype from Romania
title_short Molecular Genetic Approach and Evaluation of Cardiovascular Events in Patients with Clinical Familial Hypercholesterolemia Phenotype from Romania
title_sort molecular genetic approach and evaluation of cardiovascular events in patients with clinical familial hypercholesterolemia phenotype from romania
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036385/
https://www.ncbi.nlm.nih.gov/pubmed/33807407
http://dx.doi.org/10.3390/jcm10071399
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