Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

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Standard

Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease. / CHD Exome+ Consortium; CARDIoGRAM Exome Consortium; Global Lipids Genetics Consortium.

I: Science (New York, N.Y.), Bind 351, Nr. 6278, 11.03.2016, s. 1166-71.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

CHD Exome+ Consortium, CARDIoGRAM Exome Consortium & Global Lipids Genetics Consortium 2016, 'Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease', Science (New York, N.Y.), bind 351, nr. 6278, s. 1166-71. https://doi.org/10.1126/science.aad3517

APA

CHD Exome+ Consortium, CARDIoGRAM Exome Consortium, & Global Lipids Genetics Consortium (2016). Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease. Science (New York, N.Y.), 351(6278), 1166-71. https://doi.org/10.1126/science.aad3517

Vancouver

CHD Exome+ Consortium, CARDIoGRAM Exome Consortium, Global Lipids Genetics Consortium. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease. Science (New York, N.Y.). 2016 mar. 11;351(6278):1166-71. https://doi.org/10.1126/science.aad3517

Author

CHD Exome+ Consortium ; CARDIoGRAM Exome Consortium ; Global Lipids Genetics Consortium. / Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease. I: Science (New York, N.Y.). 2016 ; Bind 351, Nr. 6278. s. 1166-71.

Bibtex

@article{35caa05c488b4b83ae33d54846406430,
title = "Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease",
abstract = "Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant).",
keywords = "Aged, Amino Acid Substitution, Animals, Cholesterol, HDL, Coronary Disease, DNA Mutational Analysis, Female, Genetic Variation, Heterozygote, Homozygote, Humans, Leucine, Male, Mice, Middle Aged, Proline, Protein Processing, Post-Translational, Risk, Scavenger Receptors, Class B, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
author = "Paolo Zanoni and Khetarpal, {Sumeet A} and Larach, {Daniel B} and Hancock-Cerutti, {William F} and Millar, {John S} and Marina Cuchel and Stephanie DerOhannessian and Anatol Kontush and Praveen Surendran and Danish Saleheen and Stella Trompet and Jukema, {J Wouter} and {de Craen}, {Anton Jm} and Panos Deloukas and Naveed Sattar and Ian Ford and Chris Packard and Majumder, {Abdullah al Shafi} and Alam, {Dewan S} and {Di Angelantonio}, Emanuele and Goncalo Abecasis and Rajiv Chowdhury and Jeanette Erdmann and Nordestgaard, {B{\o}rge G} and Nielsen, {Sune F} and Anne Tybj{\ae}rg-Hansen and Schmidt, {Ruth Frikke} and Kari Kuulasmaa and Liu, {Dajiang J} and Markus Perola and Stefan Blankenberg and Veikko Salomaa and Satu M{\"a}nnist{\"o} and Philippe Amouyel and Dominique Arveiler and Jean Ferri{\`e}res and Martina M{\"u}ller-Nurasyid and Ferrario, {Marco M} and Frank Kee and Willer, {Cristen J} and Samani, {Nilesh J} and Heribert Schunkert and Butterworth, {Adam S} and Howson, {Joanna M. M.} and Peloso, {Gina M} and Stitziel, {Nathan O} and John Danesh and Sekar Kathiresan and Rader, {Daniel J} and {CHD Exome+ Consortium} and {CARDIoGRAM Exome Consortium} and {Global Lipids Genetics Consortium}",
note = "Copyright {\textcopyright} 2016, American Association for the Advancement of Science.",
year = "2016",
month = mar,
day = "11",
doi = "10.1126/science.aad3517",
language = "English",
volume = "351",
pages = "1166--71",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6278",

}

RIS

TY - JOUR

T1 - Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

AU - Zanoni, Paolo

AU - Khetarpal, Sumeet A

AU - Larach, Daniel B

AU - Hancock-Cerutti, William F

AU - Millar, John S

AU - Cuchel, Marina

AU - DerOhannessian, Stephanie

AU - Kontush, Anatol

AU - Surendran, Praveen

AU - Saleheen, Danish

AU - Trompet, Stella

AU - Jukema, J Wouter

AU - de Craen, Anton Jm

AU - Deloukas, Panos

AU - Sattar, Naveed

AU - Ford, Ian

AU - Packard, Chris

AU - Majumder, Abdullah al Shafi

AU - Alam, Dewan S

AU - Di Angelantonio, Emanuele

AU - Abecasis, Goncalo

AU - Chowdhury, Rajiv

AU - Erdmann, Jeanette

AU - Nordestgaard, Børge G

AU - Nielsen, Sune F

AU - Tybjærg-Hansen, Anne

AU - Schmidt, Ruth Frikke

AU - Kuulasmaa, Kari

AU - Liu, Dajiang J

AU - Perola, Markus

AU - Blankenberg, Stefan

AU - Salomaa, Veikko

AU - Männistö, Satu

AU - Amouyel, Philippe

AU - Arveiler, Dominique

AU - Ferrières, Jean

AU - Müller-Nurasyid, Martina

AU - Ferrario, Marco M

AU - Kee, Frank

AU - Willer, Cristen J

AU - Samani, Nilesh J

AU - Schunkert, Heribert

AU - Butterworth, Adam S

AU - Howson, Joanna M. M.

AU - Peloso, Gina M

AU - Stitziel, Nathan O

AU - Danesh, John

AU - Kathiresan, Sekar

AU - Rader, Daniel J

AU - CHD Exome+ Consortium

AU - CARDIoGRAM Exome Consortium

AU - Global Lipids Genetics Consortium

N1 - Copyright © 2016, American Association for the Advancement of Science.

PY - 2016/3/11

Y1 - 2016/3/11

N2 - Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant).

AB - Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant).

KW - Aged

KW - Amino Acid Substitution

KW - Animals

KW - Cholesterol, HDL

KW - Coronary Disease

KW - DNA Mutational Analysis

KW - Female

KW - Genetic Variation

KW - Heterozygote

KW - Homozygote

KW - Humans

KW - Leucine

KW - Male

KW - Mice

KW - Middle Aged

KW - Proline

KW - Protein Processing, Post-Translational

KW - Risk

KW - Scavenger Receptors, Class B

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1126/science.aad3517

DO - 10.1126/science.aad3517

M3 - Journal article

C2 - 26965621

VL - 351

SP - 1166

EP - 1171

JO - Science

JF - Science

SN - 0036-8075

IS - 6278

ER -

ID: 177525379