Compound Heterozygotes for a Novel Mutation, Apo E1 Nagoya (Arg142Ser) and Apo E2 (Arg158Cys), with Severe Type III Hyperlipoproteinemia and Familial Hypercholesterolemia

Sakuma, Nagahiko; Hibino, Takeshi; Saeki, Tomoaki; Nagata, Takahiro; Satô, Tôru; Okuda, Noriaki; Matsunaga, Akira; Sasaki, Jun

doi:10.5551/jat.21394

Cited by 3 publications

(2 citation statements)

References 22 publications

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“…Second, the location of the variant on the gene can be considered. The LDL‐R binding domain of apoE is the most vulnerable region and is located in the fourth helix, at position 180‐194 (NM_001302688.1; Supplementary Material), 28,35‐70 so when a variant is located there, the variant is more likely to be pathogenic. When using these methods it is important to note that they can never by themselves provide definite information on the causal relationship between a genetic variant and FD.…”

Section: Approaches To Establish a Causal Relation Between A New Apoe...mentioning

confidence: 99%

Establishing the relationship between familial dysbetalipoproteinemia and genetic variants in theAPOEgene

et al. 2022

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Familial Dysbetalipoproteinemia (FD) is the second most common monogenic dyslipidemia and is associated with a very high cardiovascular risk due to cholesterolenriched remnant lipoproteins. FD is usually caused by a recessively inherited variant in the APOE gene (ε2ε2), but variants with dominant inheritance have also been described. The typical dysbetalipoproteinemia phenotype has a delayed onset and requires a metabolic hit. Therefore, the diagnosis of FD should be made by demonstrating both the genotype and dysbetalipoproteinemia phenotype. Next Generation Sequencing is becoming more widely available and can reveal variants in the APOE gene for which the relation with FD is unknown or uncertain. In this article, two approaches are presented to ascertain the relationship of a new variant in the APOE gene with FD. The comprehensive approach consists of determining the pathogenicity of the variant and its causal relationship with FD by confirming a dysbetalipoproteinemia phenotype, and performing in vitro functional tests and, optionally, in vivo postprandial clearance studies. When this is not feasible, a second, pragmatic approach within reach of clinical practice can be followed for individual patients to make decisions on treatment, follow-up, and family counseling.

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Section: Approaches To Establish a Causal Relation Between A New Apoe...mentioning

confidence: 99%

Establishing the relationship between familial dysbetalipoproteinemia and genetic variants in theAPOEgene

et al. 2022

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“…Subjects with this polymorphism have reduced affinity for LDLRs, leading to low LDL cholesterol and high HDL cholesterol levels, accumulating triglyceride-rich lipoprotein containing ApoE2 in plasma, and elevation of triglycerides level [ 131 ]. Moreover, a combination of Ɛ2 with the mutation Ɛ1 Arg142Ser seems to be associated with severe type III hyperlipoproteinemia in patients with familial hypocholesterolemia [ 132 ]. Regarding Alzheimer’s disease, ApoE2 protects the brain by accumulating less amyloid β in the brain than other isoforms [ 133 , 134 ].…”

Section: Genetic Polymorphisms Alcohol Drinking and Acvd Riskmentioning

confidence: 99%

Alcohol Drinking, Apolipoprotein Polymorphisms and the Risk of Cardiovascular Diseases

Ceci

Ceccanti²,

Petrella

et al. 2021

CNR

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: Lipoprotein disorders are a major risk factor for atherosclerotic neuro-cardiovascular disease (ACVD) and are heavily influenced by lifestyle, including alcohol drinking. Moderate drinkers have a lower ACVD risk than abstainers because of their higher levels of high-density lipoprotein (HDL) cholesterol, an important protective factor against ACVD. On the contrary, heavy drinking increases ACVD risk. According to a large literature body, ethanol intoxication modifies lipid serum profile and induces endothelial dysfunction. Single nucleotide polymorphisms may influence the relationship between alcohol drinking, HDL cholesterol level, and atherosclerotic risk. The risk of ACVD in heavy drinkers seems enhanced in patients with apolipoprotein E4 allele, interleukin-6-174 polymorphism, and cholesteryl ester transfer protein TaqIB polymorphism. Apolipoprotein E4 is a known risk factor for ACVD, while apolipoprotein E2 has mixed effects. Therefore, even if a "protective role" may be attributed to moderate drinking, this effect cannot be extended to everyone.

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Dysbetalipoproteinemia

Marais

2015

Current Opinion in Lipidology

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Elevated plasma triglyceride and cholesterol concentrations (mixed hyperlipidemias) are commonly encountered and dysbetaliproteinemia should be considered in this setting. Dysbetalipoproteinemia (remnant clearance disease, Fredrickson type III hyperlipidemia) is an uncommon dyslipoproteinemia related to mutations in apolipoprotein E that disrupt the clearance of remnants of triglyceride-rich lipoproteins; it may be overlooked because xanthomata of the skin and/or tendons occur in a minority of patients. The diagnosis ideally requires the demonstration of remnant lipoprotein accumulation and a genetic cause. Genotyping for apolipoprotein E2 may not prove the diagnosis as it may be associated with low plasma lipid values. The recent association of remnant lipoproteins with atherosclerosis along with many factors that modulate remnant lipoprotein metabolism underscores the importance of recognising dysbetalipoproteinemia as an extreme state of remnant lipoprotein accumulation. Although there may be some differences between remnants in the general population and dysbetalipoproteinemia, it is clear that remnants promote atherosclerosis. Current treatment strategies are adequate but new strategies could also be of benefit in dysbetalipoproteinemia.

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Compound Heterozygotes for a Novel Mutation, Apo E1 Nagoya (Arg142Ser) and Apo E2 (Arg158Cys), with Severe Type III Hyperlipoproteinemia and Familial Hypercholesterolemia

Cited by 3 publications

References 22 publications

Establishing the relationship between familial dysbetalipoproteinemia and genetic variants in theAPOEgene

Establishing the relationship between familial dysbetalipoproteinemia and genetic variants in theAPOEgene

Alcohol Drinking, Apolipoprotein Polymorphisms and the Risk of Cardiovascular Diseases

Dysbetalipoproteinemia

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