A polymorphism in the ABCG1 promoter is functionally associated with coronary artery disease in a Chinese Han population

Xu, Yan; Wang, Wei; Zhang, Li; Qi, Liping; Li, Liyun; Chen, Lianfeng; Fang, Quan; Dang, Anhong; Yan, Xiaowei

doi:10.1016/j.atherosclerosis.2011.05.043

Cited by 59 publications

(43 citation statements)

References 30 publications

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“…Such a lack of association between ABCG1 SNPs and plasma TC, low-density lipoprotein cholesterol or HDL-cholesterol was in agreement with the analysis of the rs1378577 ABCG1 SNP in a small Japanese population of 109 male patients with coronary artery disease 13 and with a recent study analyzing 2 other ABCG1 SNPs in a large cohort of 1021 Chinese coronary artery disease patients. 22 Consistent with our findings, the absence of Abcg1 in mice was not accompanied by alteration of plasma lipid levels in Abcg1 −/− mice as compared with control animals. 2 Taken together with our data, it appears that ABCG1 indeed does not play a significant role in regulating plasma lipid metabolism in humans.…”

Section: Discussionsupporting

confidence: 92%

Human ATP–Binding Cassette G1 Controls Macrophage Lipoprotein Lipase Bioavailability and Promotes Foam Cell Formation

Olivier

Tanck

Out

et al. 2012

ATVB

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Objective— The physiological function of the ATP–binding cassette G1 (ABCG1) transporter in humans is not yet elucidated, as no genetic disease caused by ABCG1 mutations has been documented. The goal of our study was, therefore, to investigate the potential role(s) of ABCG1 in lipid metabolism in humans. Methods and Results— Here we report that among the 104 polymorphisms present in the ABCG1 gene, the analysis of the frequent functional rs1893590 and rs1378577 single nucleotide polymorphisms located in the regulatory region of ABCG1 in the Regression Growth Evaluation Statin Study population revealed that both ABCG1 single nucleotide polymorphisms were significantly associated with plasma lipoprotein lipase (LPL) activity. Moreover, we observed that plasma LPL activity was modestly reduced in Abcg1 −/− mice as compared with control mice. Adipose tissue and skeletal muscle are the major tissues accounting for levels and activity of plasma LPL in the body. However, beyond its lipolytic action in the plasma compartment, LPL was also described to act locally at the cellular level. Thus, macrophage LPL was reported to promote foam cell formation and atherosclerosis in vivo. Analysis of the relationship between ABCG1 and LPL in macrophages revealed that the knockdown of ABCG1 expression (ABCG1 knockdown) in primary cultures of human monocyte–derived macrophages using small interfering RNAs led to a marked reduction of both the secretion and activity of LPL. Indeed, LPL was trapped at the cell surface of ABCG1 knockdown human monocyte–derived macrophages, likely in cholesterol-rich domains, thereby reducing the bioavailability and activity of LPL. As a consequence, LPL–mediated lipid accumulation in human macrophage foam cells in the presence of triglyceride-rich lipoproteins was abolished when ABCG1 expression was repressed. Conclusion— We presently report that ABCG1 controls LPL activity and promotes lipid accumulation in human macrophages in the presence of triglyceride-rich lipoproteins, thereby suggesting a potential deleterious role of macrophage ABCG1 in metabolic situations associated with high levels of circulating triglyceride-rich lipoproteins together with the presence of macrophages in the arterial wall.

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Section: Discussionsupporting

confidence: 92%

Human ATP–Binding Cassette G1 Controls Macrophage Lipoprotein Lipase Bioavailability and Promotes Foam Cell Formation

Olivier

Tanck

Out

et al. 2012

ATVB

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“…These data suggest that polymorphisms that impact ABCG1 expression may play a role in regulating atherosclerosis and Treg numbers. Indeed, SNPs in the human ABCG1 promoter that reduced ABCG1 levels reduced cardiovascular risk, although these studies only focused on macrophages (49,50). It would be interesting for future studies to address whether there is a negative relationship between ABCG1 expression in Tregs and the extent of atherosclerosis in humans.…”

Section: Discussionmentioning

confidence: 99%

Loss of ABCG1 influences regulatory T cell differentiation and atherosclerosis

Cheng¹,

Gaddis²,

Wu³

et al. 2016

Journal of Clinical Investigation

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“…[11][12][13] Increased apoB levels and accelerated atherosclerosis on LDLr Variants associated with reduced and increased CAD risk in absence of effects on plasma lipids. 16,17 Cholesterol accumulation in tissues (lung); no effect on plasma lipoprotein levels. 18 Accelerated atherosclerosis in ABCA1 Both rare and common variants are associated with low or high HDL-C levels.…”

Section: Genesmentioning

confidence: 99%

Mendelian Disorders of High-Density Lipoprotein Metabolism

Oldoni

Sinke

Kuivenhoven

2014

Circulation Research

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High-density lipoproteins (HDLs) are a highly heterogeneous and dynamic group of the smallest and densest lipoproteins present in the circulation. This review provides the current molecular insight into HDL metabolism led by articles describing mutations in genes that have a large affect on HDL cholesterol levels through their roles in HDL and triglyceride metabolism. Using this information from both human and animal studies, it is discussed how HDL is produced, remodeled in the circulation, affected by factors that control the metabolism of triglyceride-rich lipoproteins, how it helps maintain cellular cholesterol homeostasis, and, finally, how it is catabolized. It can be concluded that HDL cholesterol as a trait is genetically heterogeneous, with as many as 40 genes involved. In most cases, only heterozygotes of gene variants are known, and HDL cholesterol as a trait is inherited in an autosomal-dominant manner. Only 3 Mendelian disorders of HDL metabolism are currently known, which are inherited in an autosomal-recessive mode. an overview of the knowledge that has been obtained through mutations (or targeted disruption) of these genes and illustrates the current molecular details of HDL anabolism, conversion, and catabolism. The Table summarizes how mutations in these genes may affect atheroclerosis. TerminologyDefinitions of HDL and HDL-C The mobilization of cellular cholesterol by HDL, the transport of cholesterol by HDL in the circulation, and the hepatic uptake of HDL-C are generally considered as key to the function of this lipoprotein class. However, from a biochemical perspective, HDL-C is a mere figure indicating how much cholesterol is carried by the pool of HDL in blood. Unfortunately, the terms HDL and HDL-C are often used interchangeably. This leads to confusion and sometimes wrong interpretations. In the lay literature, HDL-C is often typed as the good cholesterol, suggesting that cholesterol is beneficial as long as it is in HDL that diverts from the multiple functions that are attributed to HDL that has little if nothing to do with its cholesterol component. In this review, HDL is used when either the particle or the pool of circulating HDL is meant, whereas HDL-C refers to the free cholesterol (FC) and cholesteryl ester (CE) carried by HDL in the circulation. HDL deficiency indicates that HDL and, therefore, HDL-C are (close to) absent. In an attempt to be comprehensive, we have combined genetic insights from both animal and human studies. Finally, the terms hypoalphalipoproteinemia and hyperalphalipoproteinemia are used when HDL-C concentrations are <10th percentile or >90th percentile for age and sex, respectively. Reverse Cholesterol Transport and Cellular Cholesterol HomeostasisReverse cholesterol transport is generally used to describe the transport of cholesterol by HDL from the vascular wall to the liver for excretion into bile as neutral sterol or bile acid. Despite ≈50 years of research, there is, as of yet, little evidence that HDL can transport cholesterol from the vessel...

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A polymorphism in the ABCG1 promoter is functionally associated with coronary artery disease in a Chinese Han population

Cited by 59 publications

References 30 publications

Human ATP–Binding Cassette G1 Controls Macrophage Lipoprotein Lipase Bioavailability and Promotes Foam Cell Formation

Human ATP–Binding Cassette G1 Controls Macrophage Lipoprotein Lipase Bioavailability and Promotes Foam Cell Formation

Loss of ABCG1 influences regulatory T cell differentiation and atherosclerosis

Mendelian Disorders of High-Density Lipoprotein Metabolism

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