Funded in part by 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 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Case-control study (classified by our AI screen)
- Studied in
- People
- Main outcome
- Clinical events such as disease or death
- Intake measured by
- Not stated
Who paid for it
- Funding
- Industry funded
- Company
- Amgen
- University or hospital
- University of Michigan
- University or hospital
- NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
- Government
- National Institute for Health and Care Research
- University or hospital
- University College London
- Company
- Novo Nordisk
- Government
- NordForsk
- Company
- Novo Nordisk Fonden
- University or hospital
- College of Pharmacy, University of Michigan
- Government
- Medical Research Council
- Company
- Novo Nordisk Foundation
- University or hospital
- University College London Hospital National Institute for Health Research Biomedical Research Centre
- Company
- Novo Nordisk Foundation Center for Protein Research
- Grants
- Novo Nordisk Fonden (NNF 14CC0001); Novo Nordisk Fonden (NNF17OC0027594); Novo Nordisk (NNF17OC0027594); Novo Nordisk (NNF14CC0001); NordForsk (90580); Medical Research Council (MC_PC_17228)
Based on 13 listed funder(s).
Publication
- Published
- 2020-06-08 · Eur Heart J · vol. 41 · issue 28 · pp. 2618–2628
- Publisher
- Oxford University Press
- Cited
- 88 citations · more than 99% of similar papers · 11.7× the field average
- Impact
- Top 10% most cited in its field
- References
- 32 works
- Access
- Open access (hybrid journal) · CC-BY-NC
- Research areas
- Cholesterol and Lipid Metabolism · Drug Transport and Resistance Mechanisms · Fatty Acid Research and Health
- Keywords
- 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 authors
From IS, NL, DK, GB
- Anna Helgadóttir · correspondingdeCODE Genetics (Iceland)
- Guðmar ÞorleifssondeCODE Genetics (Iceland)
- Kristjan F. AlexanderssondeCODE Genetics (Iceland)
- Vinicius TragantedeCODE Genetics (Iceland); Utrecht University; University Medical Center Utrecht
- Margrét ÞorsteinsdóttirUniversity of Iceland; Icelandic Transport Authority
- Finnur Freyr EiríkssonIcelandic Transport Authority
Abstract
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC).
Community trust
Loading…
How much do you trust this study's findings?
Comments
Sign in to rate, comment on or flag this study.Sign inSomething wrong here?
Flag this study if its information, labels or funding look wrong. An editor reviews every flag.
Sign in to rate, comment on or flag this study.Sign inEducational information about published research. Not medical advice, and not a recommendation to start or stop anything.