Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease
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 effec...
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ftucl:oai:eprints.ucl.ac.uk.OAI2:10106796 2023-12-24T10:17:57+01:00 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 2020-07-21 text https://discovery.ucl.ac.uk/id/eprint/10106796/1/ehaa531.pdf https://discovery.ucl.ac.uk/id/eprint/10106796/ eng eng https://discovery.ucl.ac.uk/id/eprint/10106796/1/ehaa531.pdf https://discovery.ucl.ac.uk/id/eprint/10106796/ open European Heart Journal , 41 (28) pp. 2618-2628. (2020) ABCG5/8 Absorption Dietary cholesterol Genetics Phytosterols Article 2020 ftucl 2023-11-27T13:07:34Z 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. Article in Journal/Newspaper Iceland University College London: UCL Discovery |
institution |
Open Polar |
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University College London: UCL Discovery |
op_collection_id |
ftucl |
language |
English |
topic |
ABCG5/8 Absorption Dietary cholesterol Genetics Phytosterols |
spellingShingle |
ABCG5/8 Absorption Dietary cholesterol Genetics Phytosterols 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 Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease |
topic_facet |
ABCG5/8 Absorption Dietary cholesterol Genetics Phytosterols |
description |
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. |
format |
Article in Journal/Newspaper |
author |
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 |
author_facet |
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 |
author_sort |
Helgadottir, A |
title |
Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease |
title_short |
Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease |
title_full |
Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease |
title_fullStr |
Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease |
title_full_unstemmed |
Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease |
title_sort |
genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease |
publishDate |
2020 |
url |
https://discovery.ucl.ac.uk/id/eprint/10106796/1/ehaa531.pdf https://discovery.ucl.ac.uk/id/eprint/10106796/ |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
European Heart Journal , 41 (28) pp. 2618-2628. (2020) |
op_relation |
https://discovery.ucl.ac.uk/id/eprint/10106796/1/ehaa531.pdf https://discovery.ucl.ac.uk/id/eprint/10106796/ |
op_rights |
open |
_version_ |
1786206412570886144 |