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Genetic background of individuals with clinical diagnosis of FH from the Portuguese FH Study cohort

2023-05Conference object Restricted access
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dc.contributor.authorMedeiros, Ana Margarida
dc.contributor.authorAlves, Ana Catarina
dc.contributor.authorChora, Joana Rita
dc.contributor.authorMiranda, Beatriz Raposo
dc.contributor.authorBourbon, Mafalda
dc.date.accessioned2024-01-31T13:33:55Z
dc.date.available2024-01-31T13:33:55Z
dc.date.issued2023-05
dc.description.abstractAim: Familial Hypercholesterolemia (FH) is a common genetic disorder of lipid metabolism associated to increased CAD risk. Three genes are associated with FH (LDLR, APOB, PCSK9). Variants in FH phenocopies genes (LDLRAP1, APOE, LIPA, ABCG5, ABCG8), LDL-C polygenic risk score (PRS) and hyper-Lp(a) can mimic the FH phenotype. In the present work we intend to unravel the genetic background in individuals with clinical diagnosis of FH. Methods: A biochemical and genetic study was performed to 1005 patients with clinical diagnosis of FH referred to the Portuguese FH Study until December 2021. Since 2017, genetic diagnosis is performed by an NGS panel with 8 genes and 6-SNPs to determine PRS. Results: FH was genetically confirmed in 41% of the cases. In the FH-negative cohort (N=590), 30% (N=177) present Lp(a)>50mg/dl, 16% (N=95) have high PRS, 1% (N=7) have other monogenic cause and 1% (N=7) have one pathogenic variant in ABCG5/ABCG8. Additionally, 11% (N=61) carry heterozygous VUS in either LDLR, APOB or PCSK9 and 5% (N=29) carry heterozygous variants of unknown significance (VUS) in FH phenocopies genes. No identifiable cause of dyslipidemia was found in the remaining 36% patients. Conclusions: Overall, FH was confirmed genetically in 41% of the cohort. In 50% of the FH negatives the FH phenotype can be caused by Hyper-Lp(a) or high PRS. A small part of patients has pathogenic variants in ABCG5/8 in heterozygosity and this can be the cause of hypercholesterolemia and should be further investigated. This extended NGS panel is important to identify FH/FH-phenocopies and therefore personalize each patient’s treatmentpt_PT
dc.description.sponsorshipFCT grant: SFRH/BD/113017/2015; Portuguese Cardiology Society [D13123], Science and Technology Foundation [project grant PIC/IC/83333/2007]pt_PT
dc.description.versionN/Apt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/9005
dc.language.isoengpt_PT
dc.peerreviewednopt_PT
dc.publisherInstituto Nacional de Saúde Doutor Ricardo Jorge, IPpt_PT
dc.relationClinical and molecular study of familial lipoprotein disorders with increase cardiovascular risk
dc.relatione_FH. The role of epigenetics in Familial Hypercholesterolaemia phenotypes - towards a more precise medicine
dc.subjectFamilial Hypercholesterolemiapt_PT
dc.subjectFH Phenocopies Genespt_PT
dc.subjectLDL-C Polygenic Risk Scorept_PT
dc.subjectHyper-Lp apt_PT
dc.subjectDoenças Cardio e Cérebro-vascularespt_PT
dc.titleGenetic background of individuals with clinical diagnosis of FH from the Portuguese FH Study cohortpt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.awardTitleClinical and molecular study of familial lipoprotein disorders with increase cardiovascular risk
oaire.awardTitlee_FH. The role of epigenetics in Familial Hypercholesterolaemia phenotypes - towards a more precise medicine
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5646-ICCMS/PIC%2FIC%2F83333%2F2007/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F113017%2F2015/PT
oaire.citation.conferencePlaceMannheim, Germanypt_PT
oaire.citation.title91st European Atherosclerosis Society Congress, 21-24 May 2023pt_PT
oaire.fundingStream5646-ICCMS
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typeconferenceObjectpt_PT
relation.isProjectOfPublicationf7c10f58-f6f9-46f9-9663-b24e59c81818
relation.isProjectOfPublication86ef85c5-4329-4309-9bd5-6acd1938ea2c
relation.isProjectOfPublication.latestForDiscoveryf7c10f58-f6f9-46f9-9663-b24e59c81818

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