APOE polymorphism and lipid profile in three ethnic groups in the Singapore population

Tan, Chee Eng; Tai, E. Shyong; Tan, C.S.; Chia, Kee Seng; Lee, J.; Chew, Suok Kai; Ordovas, José M.

doi:10.1016/s0021-9150(03)00232-6

Cited by 87 publications

(68 citation statements)

References 27 publications

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“…Several studies suggested the association between APO E genotype and HDL-C levels. [26][27][28] We have found a similar association of APO E genotype with HDL levels in obese subjects.…”

Section: Discussionsupporting

confidence: 68%

Distribution and effect of APO E genotype on plasma lipid in non-obese and obese in north Indian population

Thakur¹

2017

jmscr

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“…Several studies suggested the association between APO E genotype and HDL-C levels. [26][27][28] We have found a similar association of APO E genotype with HDL levels in obese subjects.…”

Section: Discussionsupporting

confidence: 68%

Distribution and effect of APO E genotype on plasma lipid in non-obese and obese in north Indian population

Thakur¹

2017

jmscr

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“…Inconsistent associations between apoE genotype and fasting TAG levels have been reported in the literature (Brown & Roberts, 1991;Howard et al 1998;Bercedo-Sanz et al 1999;Inamdar et al 2000;Szalai et al 2000;Tan et al 2003), and a meta-analysis (Dallongeville et al 1992) has concluded that E2/E2, E2/E4 E2/E3 and E3/E4 subgroups have higher fasting TAG levels than E3/E3 individuals. Higher fasting TAG levels are thought to be attributable to the limited receptor affinity of the apoE2 protein present on VLDL remnants resulting in impaired hepatic clearance of TAG-rich lipoproteins.…”

Section: Apoe Genotype and Other Lipid Risk Factors For Cvdmentioning

confidence: 97%

ApoE genotype, cardiovascular risk and responsiveness to dietary fat manipulation

et al. 2007

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Cardiovascular risk is determined by the complex interactions between genetic and environmental factors. The apoE genotype represents the most-widely-studied single nucleotide polymorphism in relation to CVD risk, with > 3600 publications cited in PubMed. Although originally described as a mediator of lipoprotein metabolism, the lipoprotein-independent functions of apoE are being increasingly recognised, with limited data available on the potential impact of genotype on these metabolic processes. Furthermore, although meta-analyses suggest that apoE4 carriers may have a 40-50% increased CVD risk, the associations reported in individual studies are highly heterogeneous and it is recognised that environmental factors such as smoking status and dietary fat composition influence genotype-phenotype associations. However, information is often derived from observational studies or small intervention trials in which retrospective genotyping of the cohort results in small group sizes in the rarer E2 and E4 subgroups. Either larger well-standardised intervention trials or smaller trials with prospective recruitment according to apoE genotype are needed to fully establish the impact of diet on genotype-CVD associations and to establish the potential of dietary strategies such as reduced total fat, saturated fat, or increased antioxidant intakes to counteract the increased CVD burden in apoE4 carriers. ApoE genotype: CVD: Dietary fat: Oxidative status: InflammationThe impact of single nucleotide polymorphisms on risk of chronic diseases such as CVD, and the ability of dietary factors to manipulate genotype-phenotype associations, is being increasingly recognised. Undoubtedly, the mostwidely-studied gene variant in relation to CVD is the apoE e (e2, e3, e4) genotype. Since its discovery in 1973 the central role of the apoE protein in lipoprotein metabolism has been comprehensively investigated and reported. The 40-50 % higher risk of CVD in apoE4 carriers (Song et al. 2004) has been traditionally attributed to moderately higher circulating cholesterol and TAG levels. However, it is becoming increasingly recognised that an effect on lipoprotein metabolism alone cannot explain the disease differential and that the impact of an apoE4 genotype is largely lipoprotein independent. Roles of macrophagederived apoE protein on vascular health and atherogenesis are being identified, with apoE thought to impact on oxidative status and in an autocrine and paracrine manner affect macrophage, vascular smooth muscle cell, endothelial cell and platelet function. An impact of genotype on these localised functions of apoE could in part explain the impact of genotype on CVD pathology, as will be discussed.Additionally, apoE genotype has been shown to affect the responsiveness to the total fat content and fatty acid composition of the diet. Manipulation of dietary fat content may serve as a means of reducing the increased CVD burden associated with an apoE4 genotype.

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“…ApoB-100 and apoE were isolated from VLDL by SDS-PAGE using a Tris-glycine buffer system as described previously (8). ApoE genotypes were determined by polymerase chain reaction as described previously (9).…”

Section: Quantitation and Isolation Of Apolipoproteinsmentioning

confidence: 99%

Effects of the cholesteryl ester transfer protein inhibitor torcetrapib on VLDL apolipoprotein E metabolism

Millar

Brousseau

Diffenderfer

et al. 2008

Journal of Lipid Research

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Cholesteryl ester transfer protein (CETP) inhibition leads to changes in lipoprotein metabolism. We studied the effect of the CETP inhibitor torcetrapib on VLDL apolipoprotein E (apoE) metabolism. Subjects, pretreated with atorvastatin (n 5 9) or untreated (n 5 10), received placebo followed by torcetrapib (4 weeks each). After each treatment, subjects underwent a primed-constant infusion of D 3 -leucine to determine the VLDL apoE production rate (PR) and fractional catabolic rate (FCR). Torcetrapib alone reduced the VLDL apoE pool size (PS) (228%) by increasing the VLDL apoE FCR (77%) and leaving the VLDL apoE PR unchanged. In subjects pretreated with atorvastatin, torcetrapib increased the VLDL apoE FCR (25%) and PR (21%). This left the VLDL apoE PS unchanged but increased the VLDL apoE content, likely enhancing VLDL clearance and reducing LDL production in this group. Used alone, torcetrapib reduces the VLDL apoE PS by increasing the apoE FCR while leaving the VLDL apoE content unchanged. In contrast, torcetrapib added to atorvastatin treatment increases both the VLDL apoE FCR and PR, leaving the VLDL apoE PS unchanged. Adding torcetrapib to atorvastatin treatment increases the VLDL apoE content, likely leading to decreased conversion of VLDL to LDL, reduced LDL production, and lower levels of circulating VLDL and LDL. Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl ester from HDL to VLDL. CETP inhibitors alter lipoprotein metabolism by reducing the CETP-mediated transfer of cholesteryl ester and triglyceride between HDL and VLDL (1). The net result of this inhibition is the accumulation of cholesteryl ester in HDL and triglyceride in VLDL, thus changing both the mass and composition of these lipoproteins (2, 3). The change in lipoprotein mass and composition might be expected to alter the distribution of exchangeable apolipoproteins, including apolipoprotein E (apoE), between VLDL and HDL, because the affinity of these proteins for lipoproteins is affected by lipoprotein size and composition (4). Redistribution of apoE among lipoproteins would be expected to influence VLDL metabolism, because apoE is a ligand for the clearance of apoB-containing lipoproteins from plasma.In addition to influencing the clearance of triglyceriderich lipoproteins (chylomicrons and VLDL) from plasma, apoE has been hypothesized to influence the conversion of VLDL to LDL (5). This has been proposed to occur as a result of the preferential removal of apoE-rich VLDL and intermediate density lipoprotein (IDL) precursors of LDL. Consistent with this hypothesis, we previously reported that the apoE content of newly secreted VLDL can influence the LDL production rate (PR), with a reduced VLDL apoE content being associated with increased LDL apoB-100 production (6).The goal of the present study was to determine the effect of torcetrapib treatment on the metabolism of apoE. We conducted kinetic studies to define the mechanism(s) Manuscript

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APOE polymorphism and lipid profile in three ethnic groups in the Singapore population

Cited by 87 publications

References 27 publications

Distribution and effect of APO E genotype on plasma lipid in non-obese and obese in north Indian population

Distribution and effect of APO E genotype on plasma lipid in non-obese and obese in north Indian population

ApoE genotype, cardiovascular risk and responsiveness to dietary fat manipulation

Effects of the cholesteryl ester transfer protein inhibitor torcetrapib on VLDL apolipoprotein E metabolism

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