Forskning
Udskriv Udskriv
Switch language
Bispebjerg Hospital - en del af Københavns Universitetshospital
Udgivet

Naturally Occurring Variants in LRP1 (Low-Density Lipoprotein Receptor-Related Protein 1) Affect HDL (High-Density Lipoprotein) Metabolism Through ABCA1 (ATP-Binding Cassette A1) and SR-B1 (Scavenger Receptor Class B Type 1) in Humans

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Estimating the Population Impact of Lp(a) Lowering on the Incidence of Myocardial Infarction and Aortic Stenosis-Brief Report

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Remnant Cholesterol and Triglyceride-Rich Lipoproteins in Atherosclerosis Progression and Cardiovascular Disease

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Impact of high glucose levels and glucose lowering on risk of ischaemic stroke: a Mendelian randomisation study and meta-analysis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Elevated apolipoprotein A1 and HDL cholesterol associated with age-related macular degeneration: 2 population cohorts

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Inhibition of Cholesteryl Ester Transfer Protein Preserves High-Density Lipoprotein Cholesterol and Improves Survival in Sepsis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Association of Low Plasma Transthyretin Concentration With Risk of Heart Failure in the General Population

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Common genetic variation in MC4R does not affect atherosclerotic plaque phenotypes and cardiovascular disease outcomes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Federico Oldoni
  • Julian C van Capelleveen
  • Nawar Dalila
  • Justina C Wolters
  • Joerg Heeren
  • Richard J Sinke
  • David Y Hui
  • Geesje M Dallinga-Thie
  • Ruth Frikke-Schmidt
  • Kees G Hovingh
  • Bart van de Sluis
  • Anne Tybjærg-Hansen
  • Jan Albert Kuivenhoven
Vis graf over relationer

OBJECTIVE: Studies into the role of LRP1 (low-density lipoprotein receptor-related protein 1) in human lipid metabolism are scarce. Although it is known that a common variant in LRP1 (rs116133520) is significantly associated with HDL-C (high-density lipoprotein cholesterol), the mechanism underlying this observation is unclear. In this study, we set out to study the functional effects of 2 rare LRP1 variants identified in subjects with extremely low HDL-C levels.

APPROACH AND RESULTS: In 2 subjects with HDL-C below the first percentile for age and sex and moderately elevated triglycerides, we identified 2 rare variants in LRP1: p.Val3244Ile and p.Glu3983Asp. Both variants decrease LRP1 expression and stability. We show in a series of translational experiments that these variants culminate in reduced trafficking of ABCA1 (ATP-binding cassette A1) to the cell membrane. This is accompanied by an increase in cell surface expression of SR-B1 (scavenger receptor class B type 1). Combined these effects may contribute to low HDL-C levels in our study subjects. Supporting these findings, we provide epidemiological evidence that rs116133520 is associated with apo (apolipoprotein) A1 but not with apoB levels.

CONCLUSIONS: This study provides the first evidence that rare variants in LRP1 are associated with changes in human lipid metabolism. Specifically, this study shows that LRP1 may affect HDL metabolism by virtue of its effect on both ABCA1 and SR-B1.

OriginalsprogEngelsk
TidsskriftArteriosclerosis, Thrombosis, and Vascular Biology
Vol/bind38
Udgave nummer7
Sider (fra-til)1440-1453
Antal sider14
ISSN1079-5642
DOI
StatusUdgivet - jul. 2018

ID: 55679189