Publication
Clinical utility of the polygenic LDL-C SNP score in familial hypercholesterolemia
| dc.contributor.author | Futema, Marta | |
| dc.contributor.author | Bourbon, Mafalda | |
| dc.contributor.author | Williams, Maggie | |
| dc.contributor.author | Humphries, Steve E. | |
| dc.date.accessioned | 2018-11-14T10:35:49Z | |
| dc.date.available | 2019-11-01T01:30:15Z | |
| dc.date.issued | 2018-10 | |
| dc.description.abstract | Mutations in any of three genes (LDLR, APOB and PCSK9) are known to cause autosomal dominant FH, but a mutation can be found in only ∼40% of patients with a clinical diagnosis of FH. In the remainder, a polygenic aetiology may be the cause of the phenotype, due to the co-inheritance of common LDL-C raising variants. In 2013, we reported the development of a 12-SNP LDL-C "SNP-Score" based on common variants identified as LDL-C raising from genome wide association consortium studies, and have confirmed the validity of this score in samples of no-mutation FH adults and children from more than six countries with European-Caucasian populations. In more than 80% of those with a clinical diagnosis of FH but with no detectable mutation in LDLR/APOB/PCSK9, the polygenic explanation is the most likely for their hypercholesterolaemia. Those with a low score (in the bottom two deciles) may have a mutation in a novel gene, and further research including whole exome or whole genome sequencing is warranted. Only in families where the index case has a monogenic cause should cascade testing be carried out, using DNA tests for an unambiguous identification of affected relatives. The clinical utility of the polygenic explanation is that it supports a more conservative (less aggressive) treatment care pathway for those with no mutation. The ability to distinguish those with a clinical diagnosis of FH who have a monogenic or a polygenic cause of their hypercholesterolaemia is a paradigm example of the use of genomic information to inform Precision Medicine using lipid lowering agents with different efficacy and costs. | pt_PT |
| dc.description.sponsorship | SH is supported by a grant from the British Heart Foundation (BHF grant PG 08/008) and by funding from the Department of Health's NIHR Biomedical Research Centers funding scheme. MF is supported by the Fondation Leducq Transatlantic Networks of Excellence Program grant (no 14 CVD03). MB receives funding from strategic project grant PEst-OE/BIA/UI4046/2011. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Atherosclerosis. 2018 Oct;277:457-463. doi: 10.1016/j.atherosclerosis.2018.06.006. | pt_PT |
| dc.identifier.doi | 10.1016/j.atherosclerosis.2018.06.006 | pt_PT |
| dc.identifier.issn | 0021-9150 | |
| dc.identifier.uri | http://hdl.handle.net/10400.18/5647 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | Elsevier | pt_PT |
| dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S0021915018303162?via%3Dihub | pt_PT |
| dc.subject | Familial Hypercholesterolemia | pt_PT |
| dc.subject | LDL-C SNP-Score | pt_PT |
| dc.subject | Polygenic Hyper-cholesterolemia | pt_PT |
| dc.subject | Variants of Unknown Significance (VUS) | pt_PT |
| dc.subject | Doenças Cardio e Cérebro-vasculares | pt_PT |
| dc.title | Clinical utility of the polygenic LDL-C SNP score in familial hypercholesterolemia | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.awardURI | info:eu-repo/grantAgreement/FCT/5876/PEst-OE%2FBIA%2FUI4046%2F2014/PT | |
| oaire.citation.endPage | 463 | pt_PT |
| oaire.citation.startPage | 457 | pt_PT |
| oaire.citation.title | Atherosclerosis | pt_PT |
| oaire.citation.volume | 277 | pt_PT |
| oaire.fundingStream | 5876 | |
| project.funder.identifier | http://doi.org/10.13039/501100001871 | |
| project.funder.name | Fundação para a Ciência e a Tecnologia | |
| rcaap.rights | embargoedAccess | pt_PT |
| rcaap.type | article | pt_PT |
| relation.isProjectOfPublication | 64bb5f0b-83df-46a4-8619-8f4e4ebb35dc | |
| relation.isProjectOfPublication.latestForDiscovery | 64bb5f0b-83df-46a4-8619-8f4e4ebb35dc |
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