Financiado en parte por Amgen, Novo Nordisk, Novo Nordisk Fonden, Novo Nordisk Foundation, Novo Nordisk Foundation Center for Protein Research
Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease
Helgadottir A, Thorleifsson G, Alexandersson KF, Tragante V, Thorsteinsdottir M, Eiriksson FF, Gretarsdottir S, Björnsson E, Magnusson O, Sveinbjornsson G, Jonsdottir I, Steinthorsdottir V, Ferkingstad E, Jensson BÖ, Stefansson H, Olafsson I, Christensen AH, Torp-Pedersen C, Køber L, Pedersen OB, Erikstrup C, Sørensen E, Brunak S, Banasik K, Hansen TF, Nyegaard M, Eyjolfssson GI, Sigurdardottir O, Thorarinsson BL, Matthiasson SE, Steingrimsdottir T, Bjornsson ES, Danielsen R, Asselbergs FW, Arnar DO, Ullum H, Bundgaard H, Sulem P, Thorsteinsdottir U, Thorgeirsson G, Holm H, Gudbjartsson DF, Stefansson K
European heart journal · 74 citas
Etiquetas de revisión
Financiado por la industriaSin ajuste declarado por estilo de vidaDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Estudio de casos y controles (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
- Consumo medido con
- No se indica
Quién lo pagó
- Financiación
- Financiado por la industria
- Empresa
- Amgen
- Universidad u hospital
- University of Michigan
- Universidad u hospital
- NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
- Gobierno
- National Institute for Health and Care Research
- Universidad u hospital
- University College London
- Empresa
- Novo Nordisk
- Gobierno
- NordForsk
- Empresa
- Novo Nordisk Fonden
- Universidad u hospital
- College of Pharmacy, University of Michigan
- Gobierno
- Medical Research Council
- Empresa
- Novo Nordisk Foundation
- Universidad u hospital
- University College London Hospital National Institute for Health Research Biomedical Research Centre
- Empresa
- Novo Nordisk Foundation Center for Protein Research
- Subvenciones
- Novo Nordisk Fonden (NNF 14CC0001); Novo Nordisk Fonden (NNF17OC0027594); Novo Nordisk (NNF17OC0027594); Novo Nordisk (NNF14CC0001); NordForsk (90580); Medical Research Council (MC_PC_17228)
Según 13 financiadores declarados.
Publicación
- Publicado
- 2020-06-08 · Eur Heart J · vol. 41 · número 28 · págs. 2618–2628
- Editorial
- Oxford University Press
- Citado
- 88 citas · más que el 99% de estudios similares · 11.7× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 32 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY-NC
- Áreas de investigación
- Cholesterol and Lipid Metabolism · Drug Transport and Resistance Mechanisms · Fatty Acid Research and Health
- Palabras clave
- Medicine, Coronary artery disease, Cardiology, Internal medicine, Plant sterols, Disease, Sterol, Cholesterol
- MeSH
- humans, sterols, phytosterols, iceland, coronary artery disease, atp binding cassette transporter, subfamily g, member 5
43 autores
- Anna Helgadóttir🇮🇸 · autor de correspondenciadeCODE Genetics (Iceland)
- Guðmar Þorleifsson🇮🇸deCODE Genetics (Iceland)
- Kristjan F. Alexandersson🇮🇸deCODE Genetics (Iceland)
- Vinicius Tragante🇮🇸🇳🇱deCODE Genetics (Iceland); Utrecht University; University Medical Center Utrecht
- Margrét Þorsteinsdóttir🇮🇸University of Iceland; Icelandic Transport Authority
- Finnur Freyr Eiríksson🇮🇸Icelandic Transport Authority
- Sólveig Grétarsdóttir🇮🇸deCODE Genetics (Iceland)
- Eyþór Björnsson🇮🇸deCODE Genetics (Iceland); University of Iceland; National University Hospital of Iceland
- Ólafur Þ. Magnússon🇮🇸deCODE Genetics (Iceland)
- Garðar Sveinbjörnsson🇮🇸deCODE Genetics (Iceland)
- Ingileif Jónsdóttir🇮🇸deCODE Genetics (Iceland); University of Iceland
- Valgerður Steinthórsdóttir🇮🇸deCODE Genetics (Iceland)
- Egil Ferkingstad🇮🇸deCODE Genetics (Iceland)
- Brynjar Ö. Jensson🇮🇸deCODE Genetics (Iceland)
- Hreinn Stefánsson🇮🇸deCODE Genetics (Iceland)
- Ísleifur Ólafsson🇮🇸National University Hospital of Iceland
- Alex Hørby Christensen🇩🇰Gentofte Hospital
- Christian Tobias Torp-Pedersen🇩🇰Aalborg University Hospital; Nordsjællands Hospital
- Lars Køber🇩🇰Copenhagen University Hospital; Rigshospitalet
- Ole Birger Pedersen🇩🇰Ringsted Sygehus
- Christian Erikstrup🇩🇰Aarhus University Hospital
- Erik Sørensen🇩🇰Copenhagen University Hospital; Rigshospitalet
- Søren Brunak🇩🇰University of Copenhagen; Novo Nordisk Foundation
- Karina Banasik🇩🇰University of Copenhagen; Novo Nordisk Foundation
- Thomas Folkmann Hansen🇩🇰University of Copenhagen; Sankt Hans Hospital; Novo Nordisk Foundation; Glostrup Hospital; Rigshospitalet
- Mette Nyegaard🇩🇰Aarhus University
- Gudmundur I. Eyjolfssson
- Ólöf Sigurðardóttir🇮🇸Akureyri Hospital
- Björn Logi Þórarinsson🇮🇸National University Hospital of Iceland
- Stefán E. Matthíasson
- Þóra Steingrímsdóttir🇮🇸University of Iceland; National University Hospital of Iceland
- Einar Stefan Bjornsson🇮🇸deCODE Genetics (Iceland); University of Iceland; National University Hospital of Iceland
- Ragnar Daníelsen🇮🇸National University Hospital of Iceland
- Folkert Wouter Asselbergs🇳🇱🇬🇧Utrecht University; University Medical Center Utrecht; Health Data Research UK; University College London
- Davíð O. Arnar🇮🇸deCODE Genetics (Iceland); University of Iceland; National University Hospital of Iceland
- Henrik Ullum🇩🇰Copenhagen University Hospital; Rigshospitalet
- Henning Bundgaard🇩🇰Copenhagen University Hospital; Rigshospitalet
- Patrick Sulem🇮🇸deCODE Genetics (Iceland)
- Unnur Arna Thorsteinsdottir🇮🇸deCODE Genetics (Iceland); University of Iceland
- Guðmundur Þorgeirsson🇮🇸deCODE Genetics (Iceland); University of Iceland; National University Hospital of Iceland
- Hilma Hólm🇮🇸deCODE Genetics (Iceland)
- Daniel Fannar Gudbjartsson🇮🇸deCODE Genetics (Iceland); University of Iceland
- Kari Stefansson🇮🇸 · autor de correspondenciadeCODE Genetics (Iceland); University of Iceland
Resumen
El texto original del estudio, en el idioma en que se publicó.
Aims
To explore whether variability in dietary cholesterol and phytosterol absorption impacts the risk of coronary artery disease (CAD) using as instruments sequence variants in the ABCG5/8 genes, key regulators of intestinal absorption of dietary sterols.
Methods and results
We examined the effects of ABCG5/8 variants on non-high-density lipoprotein (non-HDL) cholesterol (N up to 610 532) and phytosterol levels (N = 3039) and the risk of CAD in Iceland, Denmark, and the UK Biobank (105 490 cases and 844 025 controls). We used genetic scores for non-HDL cholesterol to determine whether ABCG5/8 variants confer greater risk of CAD than predicted by their effect on non-HDL cholesterol. We identified nine rare ABCG5/8 coding variants with substantial impact on non-HDL cholesterol. Carriers have elevated phytosterol levels and are at increased risk of CAD. Consistent with impact on ABCG5/8 transporter function in hepatocytes, eight rare ABCG5/8 variants associate with gallstones. A genetic score of ABCG5/8 variants predicting 1 mmol/L increase in non-HDL cholesterol associates with two-fold increase in CAD risk [odds ratio (OR) = 2.01, 95% confidence interval (CI) 1.75-2.31, P = 9.8 × 10-23] compared with a 54% increase in CAD risk (OR = 1.54, 95% CI 1.49-1.59, P = 1.1 × 10-154) associated with a score of other non-HDL cholesterol variants predicting the same increase in non-HDL cholesterol (P for difference in effects = 2.4 × 10-4).
Conclusions
Genetic variation in cholesterol absorption affects levels of circulating non-HDL cholesterol and risk of CAD. Our results indicate that both dietary cholesterol and phytosterols contribute directly to atherogenesis.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY-NC).
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