Apolipoprotein E genotype as a most significant predictor of lipid response at lipid-lowering therapy: Mechanistic and clinical studies

Dergunov, Alexander D.

doi:10.1016/j.biopha.2011.04.003

Cited by 24 publications

(21 citation statements)

References 63 publications

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“…APOE plays an important role in chylomicron and very low density lipoprotein (VLDL) recycling, interacting with LDL receptors in the liver [61]. Single nucleotide variants in APOE were described as determinants for receptor interaction rates and risk factors for atherosclerosis, hypercholesterolemia or Alzheimer disease [62]. We found different APOE isoforms, like heterozygous ϵ3/ϵ2 and homozygous ϵ2 alleles in PXE patients and heterozygous ϵ3/ϵ4 in controls, in addition to the abundant homozygous ϵ3 isoform.…”

Section: Discussionmentioning

confidence: 99%

“…We found different APOE isoforms, like heterozygous ϵ3/ϵ2 and homozygous ϵ2 alleles in PXE patients and heterozygous ϵ3/ϵ4 in controls, in addition to the abundant homozygous ϵ3 isoform. The presence of at least one ϵ2 allele was associated with higher APOE levels and a lower risk for CHD, whereas at least one allele of the isoform ϵ4 was shown to predict lower APOE levels and a higher potential to develop CHD and Alzheimer disease [62]. One PXE patient was even characterized by a homozygous ϵ2 isoform of APOE, which can be a risk factor for type III hyperlipoproteinemia in 5- 10% of ϵ2 homozygous carriers [62].…”

Section: Discussionmentioning

confidence: 99%

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ABCC6- a new player in cellular cholesterol and lipoprotein metabolism?

et al. 2014

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BackgroundDysregulations in cholesterol and lipid metabolism have been linked to human diseases like hypercholesterolemia, atherosclerosis or the metabolic syndrome. Many ABC transporters are involved in trafficking of metabolites derived from these pathways. Pseudoxanthoma elasticum (PXE), an autosomal-recessive disease caused by ABCC6 mutations, is characterized by atherogenesis and soft tissue calcification.MethodsIn this study we investigated the regulation of cholesterol biosynthesis in human dermal fibroblasts from PXE patients and healthy controls.ResultsGene expression analysis of 84 targets indicated dysregulations in cholesterol metabolism in PXE fibroblasts. Transcript levels of ABCC6 were strongly increased in lipoprotein-deficient serum (LPDS) and under serum starvation in healthy controls. For the first time, increased HMG CoA reductase activities were found in PXE fibroblasts. We further observed strongly elevated transcript and protein levels for the proprotein convertase subtilisin/kexin type 9 (PCSK9), as well as a significant reduction in APOE mRNA expression in PXE.ConclusionIncreased cholesterol biosynthesis, elevated PCSK9 levels and reduced APOE mRNA expression newly found in PXE fibroblasts could enforce atherogenesis and cardiovascular risk in PXE patients. Moreover, the increase in ABCC6 expression accompanied by the induction of cholesterol biosynthesis supposes a functional role for ABCC6 in human lipoprotein and cholesterol homeostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

ABCC6- a new player in cellular cholesterol and lipoprotein metabolism?

et al. 2014

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“…In addition to cardiovascular disease, apoE gene polymorphisms were associated with many pathophysiological conditions, including Alzheimer’s disease (AD), diabetes,Parkinson’s disease, renal disease and stroke [6], [11], [25], [26], [27]. The normal role of three major isoforms of apoE is related to their receptor affinity [28].…”

Section: Discussionmentioning

confidence: 99%

Apolipoprotein E Gene Polymorphism and Risk for Coronary Heart Disease in the Chinese Population: A Meta-Analysis of 61 Studies Including 6634 Cases and 6393 Controls

Zhang

Qiao

et al. 2014

PLoS ONE

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BackgroundNumerous studies have evaluated the association between the apolipoprotein E (apoE) gene polymorphisms in coronary heart disease (CHD). However, the results remain uncertain. We carried out a meta-analysis to derive a more comprehensive estimation of the association in Chinese population.MethodsCase-control studies in Chinese and English publications were identified by searching databases of PubMed, EMBASE, Web of Science, CNKI, CBM, Wanfang, VIP and hand searching of relevant journals and the reference lists of retrieved articles. Odds ratio (OR) and 95% confidence interval (CI) were applied to assess the strength of the associations. Subgroup analysis and sensitivity analysis were performed to explore the between-study heterogeneity.ResultsWe finally identified 61 relevant studies which comprised 6634 case-patients and 6393 controls. The pooled OR for ε4 carriers was 96% higher than the ε3/3 genotype for CHD (OR, 1.96; 95% CI, 1.70 to 2.24; P<0.001). However, there was no evidence of statistically significant association between ε2 carriers and risk of CHD (OR, 1.02; 95% CI, 0.91 to 1.13; P = 0.729). In the subgroup analysis, different endpoints may partially account for the heterogeneity. No publication bias was found.ConclusionsOur meta-analysis suggests that the apoE ε4 allele may be a risk factor for CHD in the Chinese population, however, ε2 allele has no significant association.

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“…Several reports suggest that ApoE alleles influence therapy efficiency for dyslipidemias (Brisson et al, 2002; Nieminen et al, 2008; Dergunov, 2011). In fact, ApoE genotype is considered the most significant predictor of lipid response to statins and fibrates, two classes of lipid-lowering therapy which act via different mechanisms (Dergunov, 2011). While individuals with ApoE4 seem to have the poorest response to lipid-lowering therapy, individuals with ApoE2 have the highest response (Dergunov, 2011).…”

Section: Treatmentmentioning

confidence: 99%

“…In fact, ApoE genotype is considered the most significant predictor of lipid response to statins and fibrates, two classes of lipid-lowering therapy which act via different mechanisms (Dergunov, 2011). While individuals with ApoE4 seem to have the poorest response to lipid-lowering therapy, individuals with ApoE2 have the highest response (Dergunov, 2011). This result has been shown using different molecules (Ordovas et al, 1995; Nestel et al, 1997; Sanllehy et al, 1998; Ballantyne et al, 2000; Pedro-Botet et al, 2001; Zuccaro et al, 2007) and has been replicated in familial hypercholesterolemia patients (O'Malley and Illingworth, 1990; Carmena et al, 1993).…”

Section: Treatmentmentioning

confidence: 99%

The potential applications of Apolipoprotein E in personalized medicine

Villeneuve

Brisson

Marchant

et al. 2014

Front. Aging Neurosci.

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Personalized medicine uses various individual characteristics to guide medical decisions. Apolipoprotein (ApoE), the most studied polymorphism in humans, has been associated with several diseases. The purpose of this review is to elucidate the potential role of ApoE polymorphisms in personalized medicine, with a specific focus on neurodegenerative diseases, by giving an overview of its influence on disease risk assessment, diagnosis, prognosis, and therapy. This review is not a systematic inventory of the literature, but rather a summary and discussion of novel, influential and promising works in the field of ApoE research that could be valuable for personalized medicine. Empirical evidence suggests that ApoE genotype informs pre-symptomatic risk for a wide variety of diseases, is valuable for the diagnosis of type III dysbetalipoproteinemia, increases risk of dementia in neurodegenerative diseases, and is associated with a poor prognosis following acute brain damage. ApoE status appears to influence the efficacy of certain drugs, outcome of clinical trials, and might also give insight into disease prevention. Assessing ApoE genotype might therefore help to guide medical decisions in clinical practice.

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Apolipoprotein E genotype as a most significant predictor of lipid response at lipid-lowering therapy: Mechanistic and clinical studies

Cited by 24 publications

References 63 publications

ABCC6- a new player in cellular cholesterol and lipoprotein metabolism?

ABCC6- a new player in cellular cholesterol and lipoprotein metabolism?

Apolipoprotein E Gene Polymorphism and Risk for Coronary Heart Disease in the Chinese Population: A Meta-Analysis of 61 Studies Including 6634 Cases and 6393 Controls

The potential applications of Apolipoprotein E in personalized medicine

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