dc.contributor |
Háskóli Íslands (HÍ) |
dc.contributor |
University of Iceland (UI) |
dc.contributor.author |
Helgadottir, Anna |
dc.contributor.author |
sulem, patrick |
dc.contributor.author |
Thorgeirsson, Gudmundur |
dc.contributor.author |
Grétarsdóttir, Sólveig |
dc.contributor.author |
Thorleifsson, Gudmar |
dc.contributor.author |
Jensson, Brynjar Örn |
dc.contributor.author |
Arnadottir, Gudny |
dc.contributor.author |
Olafsson, Isleifur |
dc.contributor.author |
Eyjólfsson, Guðmundur I. |
dc.contributor.author |
Sigurdardottir, Olof |
dc.contributor.author |
Thorsteinsdottir, Unnur |
dc.contributor.author |
Gudbjartsson, Daniel |
dc.contributor.author |
Holm, Hilma |
dc.contributor.author |
Stefansson, Kari |
dc.date.accessioned |
2020-01-27T14:26:10Z |
dc.date.available |
2020-01-27T14:26:10Z |
dc.date.issued |
2018-03-27 |
dc.identifier.citation |
Anna Helgadottir, Patrick Sulem, Gudmundur Thorgeirsson, Solveig Gretarsdottir, Gudmar Thorleifsson, Brynjar Ö Jensson, Gudny A Arnadottir, Isleifur Olafsson, Gudmundur I Eyjolfsson, Olof Sigurdardottir, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Hilma Holm, Kari Stefansson, Rare SCARB1 mutations associate with high-density lipoprotein cholesterol but not with coronary artery disease, European Heart Journal, Volume 39, Issue 23, 14 June 2018, Pages 2172–2178, https://doi.org/10.1093/eurheartj/ehy169 |
dc.identifier.issn |
0195-668X |
dc.identifier.issn |
1522-9645 (eISSN) |
dc.identifier.uri |
https://hdl.handle.net/20.500.11815/1476 |
dc.description |
Publisher's version (útgefin grein). |
dc.description.abstract |
Aims Scavenger receptor Class B Type 1 (SR-BI) is a major receptor for high-density lipoprotein (HDL) that promotes hepatic uptake of cholesterol from HDL. A rare mutation p.P376L, in the gene encoding SR-BI, SCARB1, was recently reported to associate with elevated HDL cholesterol (HDL-C) and increased risk of coronary artery disease (CAD), suggesting that increased HDL-C caused by SR-BI impairment might be an independent marker of cardiovascular risk. We tested the hypothesis that alleles in or close to SCARB1 that associate with elevated levels of HDL-C also associate with increased risk of CAD in the relatively homogeneous population of Iceland. Methods and results Using a large resource of whole-genome sequenced Icelanders, we identified thirteen SCARB1 coding mutations that we examined for association with HDL-C (n = 136 672). Three rare SCARB1 mutations, encoding p.G319V, p.V111M, and p.V32M (combined allelic frequency = 0.2%) associate with elevated levels of HDL-C (p.G319V: β = 11.1 mg/dL, P = 8.0 × 10 -7; p.V111M: β = 8.3 mg/dL, P = 1.1 × 10 -6; p.V32M: β = 10.2 mg/dL, P = 8.1 × 10 -4). These mutations do not associate with CAD (36 886 cases/306 268 controls) (odds ratio = 0.90, 95% confidence interval 0.67-1.22, P = 0.49), despite effects on HDL-C comparable to that reported for p.P376L, both in terms of direction and magnitude. Furthermore, HDL-C raising alleles of three common SCARB1 non-coding variants, including one previously unreported (rs61941676-C: β = 1.25 mg/dL, P = 1.7 × 10 -18), and of one low frequency coding variant (p.V135I) that independently associate with higher HDL-C, do not confer increased risk of CAD. Conclusion Elevated HDL-C due to genetically compromised SR-BI function is not a marker of CAD risk. |
dc.description.sponsorship |
The authors thank all the individuals who participated in this study and whose contribution made this work possible. We also thank our valued colleagues who contributed to the data collection and phenotypic characterization of clinical samples as well as to the genotyping and analysis of the whole-genome association data.
Funding
This work was supported by deCODE genetics/Amgen. |
dc.format.extent |
2172-2178 |
dc.language.iso |
en |
dc.publisher |
Oxford University Press (OUP) |
dc.relation.ispartofseries |
European Heart Journal;39(23) |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Coronary artery disease |
dc.subject |
HDL cholesterol |
dc.subject |
Mutation |
dc.subject |
SR-BI |
dc.subject |
Coronary arteriosclerosis |
dc.subject |
Kransæðasjúkdómar |
dc.subject |
Gen |
dc.subject |
Stökkbreytingar |
dc.subject |
Kólesteról |
dc.subject |
Erfðafræði |
dc.title |
Rare SCARB1 mutations associate with high-density lipoprotein cholesterol but not with coronary artery disease |
dc.type |
info:eu-repo/semantics/article |
dcterms.license |
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
dc.description.version |
Peer Reviewed |
dc.identifier.journal |
European Heart Journal |
dc.identifier.doi |
10.1093/eurheartj/ehy169 |
dc.relation.url |
http://academic.oup.com/eurheartj/article-pdf/39/23/2172/25041378/ehy169.pdf |
dc.contributor.department |
Læknadeild (HÍ) |
dc.contributor.department |
Faculty of Medicine (UI) |
dc.contributor.school |
Heilbrigðisvísindasvið (HÍ) |
dc.contributor.school |
School of Health Sciences (UI) |
dc.contributor.school |
School of Engineering and Natural Sciences (UI) |
dc.contributor.school |
Verkfræði- og náttúruvísindasvið (HÍ) |