Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk
This review integrates historical biochemical and modern genetic findings that underpin our understanding of the low-density lipoprotein (LDL) dyslipidemias that bear on human disease. These range from life-threatening conditions of infancy through severe coronary heart disease of young adulthood, t...
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doaj-004457eb37a7421e8f2b1c85c455dc172021-04-28T05:59:14ZengElsevierJournal of Lipid Research0022-22752011-11-01521118851926Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease riskSebastiano Calandra0Patrizia Tarugi1Helen E. Speedy2Andrew F. Dean3Stefano Bertolini4Carol C. Shoulders5Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, ItalyDepartment of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, ItalyWilliam Harvey Research Institute, Queen Mary University of London, London, United KingdomHistopathology Department, Addenbrooke’s NHS Trust, Cambridge, United KingdomandDepartment of Internal Medicine, University of Genoa, Genoa, ItalyWilliam Harvey Research Institute, Queen Mary University of London, London, United Kingdom; Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy; To whom correspondence should be addressed.This review integrates historical biochemical and modern genetic findings that underpin our understanding of the low-density lipoprotein (LDL) dyslipidemias that bear on human disease. These range from life-threatening conditions of infancy through severe coronary heart disease of young adulthood, to indolent disorders of middle- and old-age. We particularly focus on the biological aspects of those gene mutations and variants that impact on sterol absorption and hepatobiliary excretion via specific membrane transporter systems (NPC1L1, ABCG5/8); the incorporation of dietary sterols (MTP) and of de novo synthesized lipids (HMGCR, TRIB1) into apoB-containing lipoproteins (APOB) and their release into the circulation (ANGPTL3, SARA2, SORT1); and receptor-mediated uptake of LDL and of intestinal and hepatic-derived lipoprotein remnants (LDLR, APOB, APOE, LDLRAP1, PCSK9, IDOL). The insights gained from integrating the wealth of genetic data with biological processes have important implications for the classification of clinical and presymptomatic diagnoses of traditional LDL dyslipidemias, sitosterolemia, and newly emerging phenotypes, as well as their management through both nutritional and pharmaceutical means.http://www.sciencedirect.com/science/article/pii/S0022227520350811intestinal sterol absorption and effluxcellular cholesterol synthesislipoprotein assemblygallstonesLDL uptake |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sebastiano Calandra Patrizia Tarugi Helen E. Speedy Andrew F. Dean Stefano Bertolini Carol C. Shoulders |
spellingShingle |
Sebastiano Calandra Patrizia Tarugi Helen E. Speedy Andrew F. Dean Stefano Bertolini Carol C. Shoulders Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk Journal of Lipid Research intestinal sterol absorption and efflux cellular cholesterol synthesis lipoprotein assembly gallstones LDL uptake |
author_facet |
Sebastiano Calandra Patrizia Tarugi Helen E. Speedy Andrew F. Dean Stefano Bertolini Carol C. Shoulders |
author_sort |
Sebastiano Calandra |
title |
Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk |
title_short |
Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk |
title_full |
Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk |
title_fullStr |
Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk |
title_full_unstemmed |
Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk |
title_sort |
mechanisms and genetic determinants regulating sterol absorption, circulating ldl levels, and sterol elimination: implications for classification and disease risk |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2011-11-01 |
description |
This review integrates historical biochemical and modern genetic findings that underpin our understanding of the low-density lipoprotein (LDL) dyslipidemias that bear on human disease. These range from life-threatening conditions of infancy through severe coronary heart disease of young adulthood, to indolent disorders of middle- and old-age. We particularly focus on the biological aspects of those gene mutations and variants that impact on sterol absorption and hepatobiliary excretion via specific membrane transporter systems (NPC1L1, ABCG5/8); the incorporation of dietary sterols (MTP) and of de novo synthesized lipids (HMGCR, TRIB1) into apoB-containing lipoproteins (APOB) and their release into the circulation (ANGPTL3, SARA2, SORT1); and receptor-mediated uptake of LDL and of intestinal and hepatic-derived lipoprotein remnants (LDLR, APOB, APOE, LDLRAP1, PCSK9, IDOL). The insights gained from integrating the wealth of genetic data with biological processes have important implications for the classification of clinical and presymptomatic diagnoses of traditional LDL dyslipidemias, sitosterolemia, and newly emerging phenotypes, as well as their management through both nutritional and pharmaceutical means. |
topic |
intestinal sterol absorption and efflux cellular cholesterol synthesis lipoprotein assembly gallstones LDL uptake |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520350811 |
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1721504655770386432 |