Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease
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 th...
Published in: | European Heart Journal |
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Language: | English |
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Oxford University Press (OUP)
2020
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Online Access: | http://dx.doi.org/10.1093/eurheartj/ehaa531 https://academic.oup.com/eurheartj/article-pdf/41/28/2618/46622543/eurheartj_41_28_2618.pdf |
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croxfordunivpr:10.1093/eurheartj/ehaa531 2024-09-09T19:47:38+00:00 Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease Helgadottir, Anna Thorleifsson, Gudmar Alexandersson, Kristjan F Tragante, Vinicius Thorsteinsdottir, Margret Eiriksson, Finnur F Gretarsdottir, Solveig Björnsson, Eythór Magnusson, Olafur Sveinbjornsson, Gardar Jonsdottir, Ingileif Steinthorsdottir, Valgerdur Ferkingstad, Egil Jensson, Brynjar Ö Stefansson, Hreinn Olafsson, Isleifur Christensen, Alex H Torp-Pedersen, Christian Køber, Lars Pedersen, Ole B Erikstrup, Christian Sørensen, Erik Brunak, Søren Banasik, Karina Hansen, Thomas F Nyegaard, Mette Eyjolfssson, Gudmundur I Sigurdardottir, Olof Thorarinsson, Bjorn L Matthiasson, Stefan E Steingrimsdottir, Thora Bjornsson, Einar S Danielsen, Ragnar Asselbergs, Folkert W Arnar, David O Ullum, Henrik Bundgaard, Henning Sulem, Patrick Thorsteinsdottir, Unnur Thorgeirsson, Gudmundur Holm, Hilma Gudbjartsson, Daniel F Stefansson, Kari Novo Nordisk Foundation University College London Hospital National Institute for Health Research Biomedical Research Centre 2020 http://dx.doi.org/10.1093/eurheartj/ehaa531 https://academic.oup.com/eurheartj/article-pdf/41/28/2618/46622543/eurheartj_41_28_2618.pdf en eng Oxford University Press (OUP) https://creativecommons.org/licenses/by-nc/4.0/ European Heart Journal volume 41, issue 28, page 2618-2628 ISSN 0195-668X 1522-9645 journal-article 2020 croxfordunivpr https://doi.org/10.1093/eurheartj/ehaa531 2024-08-27T04:16:59Z 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. Article in Journal/Newspaper Iceland Oxford University Press European Heart Journal 41 28 2618 2628 |
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Open Polar |
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Oxford University Press |
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croxfordunivpr |
language |
English |
description |
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. |
author2 |
Novo Nordisk Foundation University College London Hospital National Institute for Health Research Biomedical Research Centre |
format |
Article in Journal/Newspaper |
author |
Helgadottir, Anna Thorleifsson, Gudmar Alexandersson, Kristjan F Tragante, Vinicius Thorsteinsdottir, Margret Eiriksson, Finnur F Gretarsdottir, Solveig Björnsson, Eythór Magnusson, Olafur Sveinbjornsson, Gardar Jonsdottir, Ingileif Steinthorsdottir, Valgerdur Ferkingstad, Egil Jensson, Brynjar Ö Stefansson, Hreinn Olafsson, Isleifur Christensen, Alex H Torp-Pedersen, Christian Køber, Lars Pedersen, Ole B Erikstrup, Christian Sørensen, Erik Brunak, Søren Banasik, Karina Hansen, Thomas F Nyegaard, Mette Eyjolfssson, Gudmundur I Sigurdardottir, Olof Thorarinsson, Bjorn L Matthiasson, Stefan E Steingrimsdottir, Thora Bjornsson, Einar S Danielsen, Ragnar Asselbergs, Folkert W Arnar, David O Ullum, Henrik Bundgaard, Henning Sulem, Patrick Thorsteinsdottir, Unnur Thorgeirsson, Gudmundur Holm, Hilma Gudbjartsson, Daniel F Stefansson, Kari |
spellingShingle |
Helgadottir, Anna Thorleifsson, Gudmar Alexandersson, Kristjan F Tragante, Vinicius Thorsteinsdottir, Margret Eiriksson, Finnur F Gretarsdottir, Solveig Björnsson, Eythór Magnusson, Olafur Sveinbjornsson, Gardar Jonsdottir, Ingileif Steinthorsdottir, Valgerdur Ferkingstad, Egil Jensson, Brynjar Ö Stefansson, Hreinn Olafsson, Isleifur Christensen, Alex H Torp-Pedersen, Christian Køber, Lars Pedersen, Ole B Erikstrup, Christian Sørensen, Erik Brunak, Søren Banasik, Karina Hansen, Thomas F Nyegaard, Mette Eyjolfssson, Gudmundur I Sigurdardottir, Olof Thorarinsson, Bjorn L Matthiasson, Stefan E Steingrimsdottir, Thora Bjornsson, Einar S Danielsen, Ragnar Asselbergs, Folkert W Arnar, David O Ullum, Henrik Bundgaard, Henning Sulem, Patrick Thorsteinsdottir, Unnur Thorgeirsson, Gudmundur Holm, Hilma Gudbjartsson, Daniel F Stefansson, Kari Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease |
author_facet |
Helgadottir, Anna Thorleifsson, Gudmar Alexandersson, Kristjan F Tragante, Vinicius Thorsteinsdottir, Margret Eiriksson, Finnur F Gretarsdottir, Solveig Björnsson, Eythór Magnusson, Olafur Sveinbjornsson, Gardar Jonsdottir, Ingileif Steinthorsdottir, Valgerdur Ferkingstad, Egil Jensson, Brynjar Ö Stefansson, Hreinn Olafsson, Isleifur Christensen, Alex H Torp-Pedersen, Christian Køber, Lars Pedersen, Ole B Erikstrup, Christian Sørensen, Erik Brunak, Søren Banasik, Karina Hansen, Thomas F Nyegaard, Mette Eyjolfssson, Gudmundur I Sigurdardottir, Olof Thorarinsson, Bjorn L Matthiasson, Stefan E Steingrimsdottir, Thora Bjornsson, Einar S Danielsen, Ragnar Asselbergs, Folkert W Arnar, David O Ullum, Henrik Bundgaard, Henning Sulem, Patrick Thorsteinsdottir, Unnur Thorgeirsson, Gudmundur Holm, Hilma Gudbjartsson, Daniel F Stefansson, Kari |
author_sort |
Helgadottir, Anna |
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 |
publisher |
Oxford University Press (OUP) |
publishDate |
2020 |
url |
http://dx.doi.org/10.1093/eurheartj/ehaa531 https://academic.oup.com/eurheartj/article-pdf/41/28/2618/46622543/eurheartj_41_28_2618.pdf |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
European Heart Journal volume 41, issue 28, page 2618-2628 ISSN 0195-668X 1522-9645 |
op_rights |
https://creativecommons.org/licenses/by-nc/4.0/ |
op_doi |
https://doi.org/10.1093/eurheartj/ehaa531 |
container_title |
European Heart Journal |
container_volume |
41 |
container_issue |
28 |
container_start_page |
2618 |
op_container_end_page |
2628 |
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1809917051187232768 |