Cited by 317Cholesterol and Lipid MetabolismLipoproteins and Cardiovascular HealthLipid metabolism and disorders

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Genetic Variant of the Scavenger Receptor BI in Humans

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Vergeer, Menno, Korporaal, Suzanne J.A., Franssen, Remco, Meurs, Illiana, Out, Ruud, Hovingh, G. Kees, Hoekstra, Menno, Sierts, Jeroen A., Dallinga-Thie, Geesje M., Motazacker, Mohammad Mahdi, Holleboom, Adriaan G., Van Berkel, Theo J.C., Kastelein, John J.P., Van Eck, Miranda, Kuivenhoven, Jan Albert·2011·New England Journal of Medicine

DOI 10.1056/nejmoa0907687

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Abstract

BACKGROUND: In mice, the scavenger receptor class B type I (SR-BI) is essential for the delivery of high-density lipoprotein (HDL) cholesterol to the liver and steroidogenic organs. Paradoxically, elevated HDL cholesterol levels are associated with increased atherosclerosis in SR-BI-knockout mice. It is unclear what role SR-BI plays in human metabolism. METHODS: We sequenced the gene encoding SR-BI in persons with elevated HDL cholesterol levels and identified a family with a new missense mutation (P297S). The functional effects of the P297S mutation on HDL binding, cellular cholesterol uptake and efflux, atherosclerosis, platelet function, and adrenal function were studied. RESULTS: Cholesterol uptake from HDL by primary murine hepatocytes that expressed mutant SR-BI was reduced to half of that of hepatocytes expressing wild-type SR-BI. Carriers of the P297S mutation had increased HDL cholesterol levels (70.4 mg per deciliter [1.8 mmol per liter], vs. 53.4 mg per deciliter [1.4 mmol per liter] in noncarriers; P<0.001) and a reduced capacity for efflux of cholesterol from macrophages, but the carotid artery intima-media thickness was similar in carriers and in family noncarriers. Platelets from carriers had increased unesterified cholesterol content and impaired function. In carriers, adrenal steroidogenesis was attenuated, as evidenced by decreased urinary excretion of sterol metabolites, a decreased response to corticotropin stimulation, and symptoms of diminished adrenal function. CONCLUSIONS: We identified a family with a functional mutation in SR-BI. The mutation carriers had increased HDL cholesterol levels and a reduction in cholesterol efflux from macrophages but no significant increase in atherosclerosis. Reduced SR-BI function was associated with altered platelet function and decreased adrenal steroidogenesis. (Funded by the European Community and others.).

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Authors: Vergeer, M., Korporaal, S. J. A., Franssen, R., Meurs, I., Out, R., Hovingh, G. K., Hoekstra, M., Sierts, J. A., Dallinga-Thie, G. M., Motazacker, M. M., Holleboom, A. G., Van Berkel, T. J. C., Kastelein, J. J. P., Van Eck, M., & Kuivenhoven, J. A.
Affiliations: Amsterdam UMC Location University of Amsterdam (NL)
Leiden University (NL)
ORCID: Vergeer, Menno
Korporaal, Suzanne J.A.
Out, Ruud
Hovingh, G. Kees
Hoekstra, Menno
Motazacker, Mohammad Mahdi
Holleboom, Adriaan G.
Kastelein, John J.P.
Kuivenhoven, Jan Albert
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2011-01-13
Volume: 364
Issue: 2
Pages: 136-145
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa0907687
OpenAlex: W2077942032
Cited by: 317
References: 40
Citations by year: 2026: 7 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 18 · 2021: 17 · 2020: 14 · 2019: 19 · 2018: 17 · 2017: 29 · 2016: 14 · 2015: 29 · 2014: 34 · 2013: 34 · 2012: 31
FWCI: 42.84
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords: scavenger receptor class B type I, HDL cholesterol, high HDL cholesterol, cholesterol absorption, HDL binding, macrophage cholesterol efflux, atherosclerosis, platelet function, adrenal steroidogenesis, familial hypercholesterolemia
MeSH terms: Adolescent, Adrenal Insufficiency, Adrenal Glands, Adult, Aged, Aged, 80 and over, Animals, Carotid Arteries, Cholesterol, DNA Mutational Analysis, Female, Heterozygote, Homeostasis, Humans, Hydrocortisone, Cholesterol, HDL, Macrophages, Male, Middle Aged, Pedigree, Triglycerides, Platelet Activation, Mice, Knockout, Mutation, Missense, Atherosclerosis, Scavenger Receptors, Class B, Mice, Young Adult

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Genetic Variant of the Scavenger Receptor BI in Humans

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