Evidence map›Paper›PMID 27651445›Full record

ArticleCirculation. Cardiovascular genetics2016

SCARB1 Gene Variants Are Associated With the Phenotype of Combined High High-Density Lipoprotein Cholesterol and High Lipoprotein (a).

Xiaoping Yang, Amar Sethi, Lisa R Yanek, Cathy Knapper, Børge G Nordestgaard, Anne Tybjærg-Hansen, Diane M Becker, Rasika A Mathias, Alan T Remaley, Lewis C Becker

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation. Cardiovascular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Lipoprotein(a) and cardiovascular disease.The Biochemical journal · 2024
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Genomic Variants and Multilevel Regulation ofJournal of cardiovascular development and disease · 2021
    Review
  13. High-Density Lipoproteins in Kidney Disease.International journal of molecular sciences · 2021
    Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Xiaoping YangFrom the Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD (X.Y., L.R.Y., D.M.B., R.A.M., L.C.B.); Lipoprotein Metabolism Section, Pulmonary and Vascular Medicine Branch, NHLBI, National Institutes of Health, Bethesda, MD (A.S., C.K., A.T.R.); and Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark (B.G.N., A.T.-H.).
Amar SethiFrom the Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD (X.Y., L.R.Y., D.M.B., R.A.M., L.C.B.); Lipoprotein Metabolism Section, Pulmonary and Vascular Medicine Branch, NHLBI, National Institutes of Health, Bethesda, MD (A.S., C.K., A.T.R.); and Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark (B.G.N., A.T.-H.).
Lisa R YanekFrom the Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD (X.Y., L.R.Y., D.M.B., R.A.M., L.C.B.); Lipoprotein Metabolism Section, Pulmonary and Vascular Medicine Branch, NHLBI, National Institutes of Health, Bethesda, MD (A.S., C.K., A.T.R.); and Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark (B.G.N., A.T.-H.).
Cathy KnapperFrom the Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD (X.Y., L.R.Y., D.M.B., R.A.M., L.C.B.); Lipoprotein Metabolism Section, Pulmonary and Vascular Medicine Branch, NHLBI, National Institutes of Health, Bethesda, MD (A.S., C.K., A.T.R.); and Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark (B.G.N., A.T.-H.).
Børge G NordestgaardFrom the Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD (X.Y., L.R.Y., D.M.B., R.A.M., L.C.B.); Lipoprotein Metabolism Section, Pulmonary and Vascular Medicine Branch, NHLBI, National Institutes of Health, Bethesda, MD (A.S., C.K., A.T.R.); and Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark (B.G.N., A.T.-H.).
Anne Tybjærg-HansenFrom the Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD (X.Y., L.R.Y., D.M.B., R.A.M., L.C.B.); Lipoprotein Metabolism Section, Pulmonary and Vascular Medicine Branch, NHLBI, National Institutes of Health, Bethesda, MD (A.S., C.K., A.T.R.); and Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark (B.G.N., A.T.-H.).
Diane M BeckerFrom the Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD (X.Y., L.R.Y., D.M.B., R.A.M., L.C.B.); Lipoprotein Metabolism Section, Pulmonary and Vascular Medicine Branch, NHLBI, National Institutes of Health, Bethesda, MD (A.S., C.K., A.T.R.); and Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark (B.G.N., A.T.-H.).
Rasika A MathiasFrom the Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD (X.Y., L.R.Y., D.M.B., R.A.M., L.C.B.); Lipoprotein Metabolism Section, Pulmonary and Vascular Medicine Branch, NHLBI, National Institutes of Health, Bethesda, MD (A.S., C.K., A.T.R.); and Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark (B.G.N., A.T.-H.).
Alan T RemaleyFrom the Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD (X.Y., L.R.Y., D.M.B., R.A.M., L.C.B.); Lipoprotein Metabolism Section, Pulmonary and Vascular Medicine Branch, NHLBI, National Institutes of Health, Bethesda, MD (A.S., C.K., A.T.R.); and Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark (B.G.N., A.T.-H.).
Lewis C BeckerFrom the Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD (X.Y., L.R.Y., D.M.B., R.A.M., L.C.B.); Lipoprotein Metabolism Section, Pulmonary and Vascular Medicine Branch, NHLBI, National Institutes of Health, Bethesda, MD (A.S., C.K., A.T.R.); and Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Denmark (B.G.N., A.T.-H.). lbecker@jhmi.edu.
Johns Hopkins University · US

Funding

Stat3 in Post-Ischemic Myocardial InflammationP01HL065608 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI BECKER, LEWIS C · 2000 to 2011
$22.0M
Genotypic Determinants of Aspirin Response in High Risk FamiliesU01HL072518 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI BECKER, LEWIS C · 2002 to 2008
$12.8M
A Family-based Exome Sequencing Approach to Identify Platelet Aggregation GenesR01HL112064 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MATHIAS, RASIKA ANN · 2012 to 2015
$5.1M
Nurse Model in Black Families at Risk for Heart DiseaseR01NR008153 · NINR · JOHNS HOPKINS UNIVERSITY · PI BECKER, DIANE M · 2002 to 2005
$2.2M
DETERMINANTS OF CORONARY DISEASE IN HIGH RISK FAMILIESR01HL059684 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI BECKER, LEWIS C · 1998 to 2001
$1.1M
NHLBI NIH HHS P01 HL065608NHLBI NIH HHS R01 HL059684NHLBI NIH HHS R01 HL112064NHLBI NIH HHS U01 HL072518NINR NIH HHS R01 NR008153
6 · The paper itself

Abstract

backgroundSR-B1 (scavenger receptor class B type 1), encoded by the gene SCARB1, is a lipoprotein receptor that binds both high-density lipoprotein (HDL) and low-density lipoprotein. We reported that SR-B1 is also a receptor for lipoprotein (a) (Lp(a)), mediating cellular uptake of Lp(a) in vitro and promoting clearance of Lp(a) in vivo. Although genetic variants in SCARB1 are associated with variations in HDL level, no SCARB1 variants affecting Lp(a) have been reported. METHODS AND

resultsIn an index subject with high levels of HDL cholesterol and Lp(a), SCARB1 was sequenced and demonstrated a missense mutation resulting in an S129L substitution in exon 3. To follow up, 2 cohorts (GeneSTAR, the family-based Genetic Study of Atherosclerosis Risk [n=543], and CCHS, the population-based Copenhagen City Heart Study [n=5835]) were screened for combined HDL cholesterol and Lp(a) elevations. Subjects with the extreme phenotype (HDL >80 mg/dL and Lp(a) >100 nmol/L in GeneSTAR, n=8, and >100 mg/dL in CCHS, n=9) underwent sequencing of SCARB1 exons; 15 of 18 from the combined population demonstrated genetic variants, including rare or uncommon missense or splice site mutations in 9 and homozygous synonymous variants in 6. Functional studies with 4 of the SCARB1 variants (c.386C>T, c.631-14T>G, c.4G>A, and c.631-53

conclusionsHuman SCARB1 gene variants are associated with a new lipid phenotype, characterized by high levels of both HDL cholesterol and Lp(a). SCARB1 exonic variants often result in diminished function of translated SR-B1 via reduced binding/intracellular transport of Lp(a).

Indexed as

Mutation, MissenseAcute Coronary SyndromeAdultAgedAmino Acid SubstitutionAtherosclerosisBiomarkersCase-Control StudiesCholesterol, HDLDenmarkDyslipidemiasExonsFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHEK293 CellsBiomarkersCholesterol, HDLLipoprotein(a)SCARB1 protein, humanScavenger Receptors, Class BCopenhagen City Heart StudyGeneSTARhigh-density lipoprotein cholesterollipids and lipoproteinslipoprotein (a)SCARB1 gene variantsSR-B1 receptor

Identifiers

PMID27651445
PMCPMC12199906
OpenAlexW2536697008

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.