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Preliminary spectrum of genetic variants in familial hypercholesterolemia in Argentina

2017-03Journal article Restricted access
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dc.contributor.authorBañares, V.G.
dc.contributor.authorCorral, P.
dc.contributor.authorMedeiros, A.M.
dc.contributor.authorAraujo, M.B.
dc.contributor.authorLozada, A.
dc.contributor.authorBustamante, J.
dc.contributor.authorCerretini, R.
dc.contributor.authorLópez, G.
dc.contributor.authorBourbon, M.
dc.contributor.authorSchreier, L.E.
dc.date.accessioned2017-11-03T15:54:27Z
dc.date.available2021-03-01T01:30:12Z
dc.date.issued2017-03
dc.description.abstractHighlights: - 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.pt_PT
dc.description.sponsorshipThe 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Clin Lipidol. 2017 Mar - Apr;11(2):524-531. doi: 10.1016/j.jacl.2017.02.007. Epub 2017 Feb 28.pt_PT
dc.identifier.doi10.1016/j.jacl.2017.02.007pt_PT
dc.identifier.issn1933-2874
dc.identifier.urihttp://hdl.handle.net/10400.18/4805
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevier/ National Lipid Associationpt_PT
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S1933287417300338pt_PT
dc.subjectAPOBpt_PT
dc.subjectArgentinapt_PT
dc.subjectCardiovascular Diseasept_PT
dc.subjectCardiovascular Disease Preventionpt_PT
dc.subjectCholesterolpt_PT
dc.subjectFamilial Hypercholesterolemiapt_PT
dc.subjectGenetic Variantspt_PT
dc.subjectLDLR genept_PT
dc.subjectMutationspt_PT
dc.subjectPublic Healthpt_PT
dc.subjectDoenças Cardio e Cérebro-vascularespt_PT
dc.titlePreliminary spectrum of genetic variants in familial hypercholesterolemia in Argentinapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage531pt_PT
oaire.citation.issue2pt_PT
oaire.citation.startPage524pt_PT
oaire.citation.titleJournal of Clinical Lipidologypt_PT
oaire.citation.volume11pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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