Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina
Main Author: | |
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Publication Date: | 2017 |
Other Authors: | , , , , , , , , |
Format: | Article |
Language: | eng |
Source: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Download full: | http://hdl.handle.net/10400.18/4805 |
Summary: | Highlights: - First description of familial hypercholesterolemia mutations in Argentina; - Identification of 7 patients with severe familial hypercholesterolemia; - Wide genetic heterogeneity with 1 relatively common allele, the Lebanese mutation; Description and deep bioinformatics characterization of 4 novel genetic variants; - Studying the exon 14 in a first step could be a low-cost approach for this population. Background: Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol and early cardiovascular disease. As cardiovascular disease is a leading cause of mortality in Argentina, early identification of patients with FH is of great public health importance. Objective: The aim of our study was to identify families with FH and to approximate to the characterization of the genetic spectrum mutations of FH in Argentina. Methods: Thirty-three not related index cases were selected with clinical diagnosis of FH. Genetic analysis was performed by sequencing, multiplex ligation-dependent probe amplification, and bioinformatics tools. Results: Twenty genetic variants were identified among 24 cases (73%), 95% on the low-density lipoprotein receptor gene. The only variant on APOB was the R3527Q. Four were novel variants: c.-135C>A, c.170A>C p.(Asp57Ala), c.684G>C p.(Glu228Asp), and c.1895A>T p.(Asn632Ile); the bioinformatics’ analysis revealed clear destabilizing effects for 2 of them. The exon 14 presented the highest number of variants (32%). Four variants were observed in more than 1 case and the c.2043C>A p.(Cys681*) was carried by 18% of index cases. Two true homozygotes, 3 compound heterozygotes, and 1 double heterozygote were identified. Conclusion: This study characterizes for the first time in Argentina genetic variants associated with FH and suggest that the allelic heterogeneity of the FH in the country could have 1 relative common low-density lipoprotein receptor mutation. This knowledge is important for the genotype–phenotype correlation and for optimizing both cholesterol-lowering therapies and mutational analysis protocols. In addition, these data contribute to the understanding of the molecular basis of FH in Argentina. |
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Preliminary spectrum of genetic variants in familial hypercholesterolemia in ArgentinaAPOBArgentinaCardiovascular DiseaseCardiovascular Disease PreventionCholesterolFamilial HypercholesterolemiaGenetic VariantsLDLR geneMutationsPublic HealthDoenças Cardio e Cérebro-vascularesHighlights: - First description of familial hypercholesterolemia mutations in Argentina; - Identification of 7 patients with severe familial hypercholesterolemia; - Wide genetic heterogeneity with 1 relatively common allele, the Lebanese mutation; Description and deep bioinformatics characterization of 4 novel genetic variants; - Studying the exon 14 in a first step could be a low-cost approach for this population. Background: Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol and early cardiovascular disease. As cardiovascular disease is a leading cause of mortality in Argentina, early identification of patients with FH is of great public health importance. Objective: The aim of our study was to identify families with FH and to approximate to the characterization of the genetic spectrum mutations of FH in Argentina. Methods: Thirty-three not related index cases were selected with clinical diagnosis of FH. Genetic analysis was performed by sequencing, multiplex ligation-dependent probe amplification, and bioinformatics tools. Results: Twenty genetic variants were identified among 24 cases (73%), 95% on the low-density lipoprotein receptor gene. The only variant on APOB was the R3527Q. Four were novel variants: c.-135C>A, c.170A>C p.(Asp57Ala), c.684G>C p.(Glu228Asp), and c.1895A>T p.(Asn632Ile); the bioinformatics’ analysis revealed clear destabilizing effects for 2 of them. The exon 14 presented the highest number of variants (32%). Four variants were observed in more than 1 case and the c.2043C>A p.(Cys681*) was carried by 18% of index cases. Two true homozygotes, 3 compound heterozygotes, and 1 double heterozygote were identified. Conclusion: This study characterizes for the first time in Argentina genetic variants associated with FH and suggest that the allelic heterogeneity of the FH in the country could have 1 relative common low-density lipoprotein receptor mutation. This knowledge is important for the genotype–phenotype correlation and for optimizing both cholesterol-lowering therapies and mutational analysis protocols. In addition, these data contribute to the understanding of the molecular basis of FH in Argentina.The authors thank the support from University of Buenos Aires, Argentina, UBACyT-B093 and from the Centro Nacional de Genetica Medica, ANLIS ‘‘Dr. Carlos Malbram,’’ Argentina.Elsevier/ National Lipid AssociationRepositório Científico do Instituto Nacional de SaúdeBañares, V.G.Corral, P.Medeiros, A.M.Araujo, M.B.Lozada, A.Bustamante, J.Cerretini, R.López, G.Bourbon, M.Schreier, L.E.2021-03-01T01:30:12Z2017-032017-03-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/4805engJ Clin Lipidol. 2017 Mar - Apr;11(2):524-531. doi: 10.1016/j.jacl.2017.02.007. Epub 2017 Feb 28.1933-287410.1016/j.jacl.2017.02.007info: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:RCAAP2023-07-20T15:40:29Zoai:repositorio.insa.pt:10400.18/4805Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:39:30.553537Repositório 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 |
Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina |
title |
Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina |
spellingShingle |
Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina Bañares, V.G. APOB Argentina Cardiovascular Disease Cardiovascular Disease Prevention Cholesterol Familial Hypercholesterolemia Genetic Variants LDLR gene Mutations Public Health Doenças Cardio e Cérebro-vasculares |
title_short |
Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina |
title_full |
Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina |
title_fullStr |
Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina |
title_full_unstemmed |
Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina |
title_sort |
Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina |
author |
Bañares, V.G. |
author_facet |
Bañares, V.G. Corral, P. Medeiros, A.M. Araujo, M.B. Lozada, A. Bustamante, J. Cerretini, R. López, G. Bourbon, M. Schreier, L.E. |
author_role |
author |
author2 |
Corral, P. Medeiros, A.M. Araujo, M.B. Lozada, A. Bustamante, J. Cerretini, R. López, G. Bourbon, M. Schreier, L.E. |
author2_role |
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 |
Bañares, V.G. Corral, P. Medeiros, A.M. Araujo, M.B. Lozada, A. Bustamante, J. Cerretini, R. López, G. Bourbon, M. Schreier, L.E. |
dc.subject.por.fl_str_mv |
APOB Argentina Cardiovascular Disease Cardiovascular Disease Prevention Cholesterol Familial Hypercholesterolemia Genetic Variants LDLR gene Mutations Public Health Doenças Cardio e Cérebro-vasculares |
topic |
APOB Argentina Cardiovascular Disease Cardiovascular Disease Prevention Cholesterol Familial Hypercholesterolemia Genetic Variants LDLR gene Mutations Public Health Doenças Cardio e Cérebro-vasculares |
description |
Highlights: - First description of familial hypercholesterolemia mutations in Argentina; - Identification of 7 patients with severe familial hypercholesterolemia; - Wide genetic heterogeneity with 1 relatively common allele, the Lebanese mutation; Description and deep bioinformatics characterization of 4 novel genetic variants; - Studying the exon 14 in a first step could be a low-cost approach for this population. Background: Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol and early cardiovascular disease. As cardiovascular disease is a leading cause of mortality in Argentina, early identification of patients with FH is of great public health importance. Objective: The aim of our study was to identify families with FH and to approximate to the characterization of the genetic spectrum mutations of FH in Argentina. Methods: Thirty-three not related index cases were selected with clinical diagnosis of FH. Genetic analysis was performed by sequencing, multiplex ligation-dependent probe amplification, and bioinformatics tools. Results: Twenty genetic variants were identified among 24 cases (73%), 95% on the low-density lipoprotein receptor gene. The only variant on APOB was the R3527Q. Four were novel variants: c.-135C>A, c.170A>C p.(Asp57Ala), c.684G>C p.(Glu228Asp), and c.1895A>T p.(Asn632Ile); the bioinformatics’ analysis revealed clear destabilizing effects for 2 of them. The exon 14 presented the highest number of variants (32%). Four variants were observed in more than 1 case and the c.2043C>A p.(Cys681*) was carried by 18% of index cases. Two true homozygotes, 3 compound heterozygotes, and 1 double heterozygote were identified. Conclusion: This study characterizes for the first time in Argentina genetic variants associated with FH and suggest that the allelic heterogeneity of the FH in the country could have 1 relative common low-density lipoprotein receptor mutation. This knowledge is important for the genotype–phenotype correlation and for optimizing both cholesterol-lowering therapies and mutational analysis protocols. In addition, these data contribute to the understanding of the molecular basis of FH in Argentina. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-03 2017-03-01T00:00:00Z 2021-03-01T01:30:12Z |
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/10400.18/4805 |
url |
http://hdl.handle.net/10400.18/4805 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
J Clin Lipidol. 2017 Mar - Apr;11(2):524-531. doi: 10.1016/j.jacl.2017.02.007. Epub 2017 Feb 28. 1933-2874 10.1016/j.jacl.2017.02.007 |
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 |
Elsevier/ National Lipid Association |
publisher.none.fl_str_mv |
Elsevier/ National Lipid 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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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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) |
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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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1799132134426804224 |