Sequencing and functional characterization of SCARB1 variants in subjects with extreme HDL cholesterol levels.
• SCARB1 was sequenced in 96 extreme-high-density lipoprotein cholesterol (HDL-C) subjects; 25 variants identified. • Novel c.-177G>T promoter and missense p.(Thr118Ser) were described. • p.(Thr118Ser) and p.(Thr378Met) co-segregate with high HDL-C. • p.(Thr378Met) variant impairs SR-B1–mediated HDL...
| Publicado en: | Journal of Clinical Lipidology Vol. 20; no. 2; pp. 389 - 402 |
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| Autores principales: | , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Elsevier B.V.
Feb2026
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=191980779&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 191980779 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 19332874 54Y0 jtl: Journal of Clinical Lipidology issn: 19332874 maglogo: N pubinfo: dt: Feb2026 vid: 20 iid: 2 pid: 467 pub: Elsevier B.V. place: New York, New York artinfo: ui: 191980779 10.1016/j.jacl.2025.11.017 191980779 ppf: 389 ppct: 13 formats: tig: atl: Sequencing and functional characterization of SCARB1 variants in subjects with extreme HDL cholesterol levels. aug: au: Gracia-Rubio, Irene Benito-Vicente, Asier Lamiquiz-Moneo, Itziar Bea, Ana María Marco-Benedí, Victoria Cabrera-Antón, Endika Martín, César Civeira, Fernando Cenarro, Ana affil: Unidad Clínica y de Investigación en Lípidos y Arteriosclerosis, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza. Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain sug: subj: Lipoproteins, HDL Cholesterol Blood Sequence Analysis Gene Expression Antigens, Surface Physiology Receptors, Cell Surface Physiology Antigens, Surface Analysis Receptors, Cell Surface Analysis Human Lipoproteins, HDL Cholesterol Analysis Cardiac Patients Phenotype Biochemistry Anthropometry Bioinformatics Flow Cytometry Triglycerides Body Mass Index Coronary Arteriosclerosis Risk Factors ab: • SCARB1 was sequenced in 96 extreme-high-density lipoprotein cholesterol (HDL-C) subjects; 25 variants identified. • Novel c.-177G>T promoter and missense p.(Thr118Ser) were described. • p.(Thr118Ser) and p.(Thr378Met) co-segregate with high HDL-C. • p.(Thr378Met) variant impairs SR-B1–mediated HDL uptake in vitro. Rare variants in SCARB1 , which encodes the high-density lipoprotein (HDL) receptor scavenger receptor class B type 1 (SR-B1), are hypothesized to drive unexplained extreme levels of plasma HDL cholesterol (HDL-C). We sequenced and phenotypically correlated SCARB1 by analyzing individuals with extreme HDL-C levels and characterizing the functional consequences of rare identified variants. SCARB1 was Sanger-sequenced in 96 unrelated participants with extreme HDL-C levels. Clinical, biochemical, and anthropometric data were compared between groups. Bioinformatic tools were used to predict the functional impact of all detected variants. Familial analyses of predicted damaging in silico or not previously described variants was assessed, and HDL uptake was quantified by flow cytometry in HEK293 cells expressing rare SCARB1 variants showing a suggestive pattern of familial segregation. Compared with the high-HDL-C group, low-HDL-C subjects exhibited lower low-density lipoprotein cholesterol and total cholesterol but higher triglycerides, higher body mass index, and a greater frequency of atherosclerotic cardiovascular disease events. Twenty-five SCARB1 variants were identified; 4 of them, c.-177G>T, p.(Thr118Ser), c.843-982G>A and p.(Thr378Met), were predicted to be deleterious. The missense changes p.(Thr118Ser) and p.(Thr378Met) showed a suggestive pattern of segregation with high HDL-C in available pedigrees. Cells expressing p.(Thr378Met) SCARB1 variant showed a reduction in HDL uptake vs wild-type. Rare predicted damaging in silico variant in SCARB1 , p.(Thr378Met), impairs SR-B1-mediated HDL uptake and associates with high HDL-C levels, highlighting SCARB1 as a candidate gene for genetic screening in dyslipidemic patients. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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