Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease

Research output: Contribution to journalJournal articleResearchpeer-review

  1. The European Heart Journal: leading the fight to reduce the global burden of cardiovascular disease

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Sudden cardiac death among persons with diabetes aged 1-49 years: a 10-year nationwide study of 14 294 deaths in Denmark

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Sudden death in heart failure: do we understand what we observe?

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. A phenome-wide association and Mendelian Randomisation study of polygenic risk for depression in UK Biobank

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Prevalence and incidence of various Cancer subtypes in patients with heart failure vs matched controls

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Coronary risk of patients with valvular heart disease: prospective validation of CT-Valve Score

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Self-reported health status and the associated risk of mortality in heart failure: The DANISH trial

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Differences in mortality in patients undergoing surgery for infective endocarditis according to age and valvular surgery

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Anna Helgadottir
  • Gudmar Thorleifsson
  • Kristjan F Alexandersson
  • Vinicius Tragante
  • Margret Thorsteinsdottir
  • Finnur F Eiriksson
  • Solveig Gretarsdottir
  • Eythór Björnsson
  • Olafur Magnusson
  • Gardar Sveinbjornsson
  • Ingileif Jonsdottir
  • Valgerdur Steinthorsdottir
  • Egil Ferkingstad
  • Brynjar Ö Jensson
  • Hreinn Stefansson
  • Isleifur Olafsson
  • Alex H Christensen
  • Christian Torp-Pedersen
  • Lars Køber
  • Ole B Pedersen
  • Christian Erikstrup
  • Erik Sørensen
  • Søren Brunak
  • Karina Banasik
  • Thomas F Hansen
  • Mette Nyegaard
  • Gudmundur I Eyjolfssson
  • Olof Sigurdardottir
  • Bjorn L Thorarinsson
  • Stefan E Matthiasson
  • Thora Steingrimsdottir
  • Einar S Bjornsson
  • Ragnar Danielsen
  • Folkert W Asselbergs
  • David O Arnar
  • Henrik Ullum
  • Henning Bundgaard
  • Patrick Sulem
  • Unnur Thorsteinsdottir
  • Gudmundur Thorgeirsson
  • Hilma Holm
  • Daniel F Gudbjartsson
  • Kari Stefansson
View graph of relations

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.

Original languageEnglish
JournalEuropean Heart Journal
Volume41
Issue number28
Pages (from-to)2618-2628
Number of pages11
ISSN0195-668X
DOIs
Publication statusPublished - 2020

ID: 60567896