Adiposity and the development of dyslipidemia in APOE ε2 homozygous subjects: A longitudinal analysis in two population-based cohorts

Heidemann, Britt E; Wolters, Frank J.; Kavousi, Maryam; Gruppen, Eke G.; Dullaart, Robin P. F.; Marais, A. David; Visseren, Frank L J; Koopal, Charlotte

doi:10.1016/j.atherosclerosis.2021.04.001

Cited by 10 publications

(5 citation statements)

References 33 publications

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“…Additional factors are required. These factors are highly diverse, and their contribution to the development of FD is still being studied [8]. Furthermore, genetically based hyperlipidemias may exhibit similar phenotypic features.…”

Section: Applicability Of Biochemical Fd Criteria For Identifying Sub...mentioning

confidence: 99%

“…Additional factors leading to increased synthesis of very-low-density lipoproteins or impaired excretion of lipoprotein remnants, including impaired functioning of the heparan sulfate proteoglycan receptor, are necessary. These factors include overweight or obesity [3,7,8], insulin resistance [3,7,9], diabetes mellitus [3,10], hypothyroidism, some medications, menopause [3], and pregnancy [11,12]. In the presence of these conditions, inhibition or even degradation of the heparan sulfate proteoglycan receptor can occur, leading to the accumulation of remnants and the development of FD [3].…”

Section: Introductionmentioning

confidence: 99%

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Applicability of Diagnostic Criteria and High Prevalence of Familial Dysbetalipoproteinemia in Russia: A Pilot Study

Blokhina,

Ershova,

Kiseleva

et al. 2023

IJMS

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Familial dysbetalipoproteinemia (FD) is a highly atherogenic genetically based lipid disorder with an underestimated actual prevalence. In recent years, several biochemical algorithms have been developed to diagnose FD using available laboratory tests. The practical applicability of FD diagnostic criteria and the prevalence of FD in Russia have not been previously assessed. We demonstrated that the diagnostic algorithms of FD, including the diagnostic apoB levels, require correction, taking into account the distribution of apoB levels in the population. At the same time, a triglycerides cutoff ≥ 1.5 mmol/L may be a useful tool in identifying subjects with FD. In this study, a high prevalence of FD was detected: 0.67% (one in 150) based on the ε2ε2 haplotype and triglycerides levels ≥ 1.5 mmol/L. We also analyzed the presence and pathogenicity of APOE variants associated with autosomal dominant FD in a large research sample.

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Section: Applicability Of Biochemical Fd Criteria For Identifying Sub...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Applicability of Diagnostic Criteria and High Prevalence of Familial Dysbetalipoproteinemia in Russia: A Pilot Study

Blokhina,

Ershova,

Kiseleva

et al. 2023

IJMS

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“…Rarely, hepatic lipase deficiency is responsible for a similar dysbetalipoproteinemia phenotype 6 . Generally, only 10%–15% of people with an ɛ2ɛ2 genotype develop the specific dysbetalipoproteinemia phenotype later in life, involving additional metabolic stress, usually obesity, insulin resistance or diabetes mellitus 7,8 . FD has a genetic background and is therefore hereditary, but in most cases it is a recessive disorder, with a low penetrance.…”

Section: Introductionmentioning

confidence: 99%

“…6 Generally, only 10%-15% of people with an ϵ2ϵ2 genotype develop the specific dysbetalipoproteinemia phenotype later in life, involving additional metabolic stress, usually obesity, insulin resistance or diabetes mellitus. 7,8 FD has a genetic background and is therefore hereditary, but in most cases it is a recessive disorder, with a low penetrance. So although FD is a genetic disease, the disorder does not usually run in the family and is therefore not "familial."…”

Section: Introductionmentioning

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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“…It is thought that the remaining 10% of the cases are caused by an autosomal dominant mutation in the APOE gene such as the apoE3 Leiden mutation [2]. However, the penetrance of the genetic susceptibility in DBL is low and the presence of secondary factors (metabolic stress) is required to precipitate the disease, which includes adiposity, diabetes or metabolic syndrome [3 ▪ ]. Accordingly, not all individuals presenting the E2/E2 genotype will develop DBL, and the clinical phenotype of the disease often appears during adulthood, generally not before the third or fourth decade of life.…”

Section: Introductionmentioning

confidence: 99%

Diagnosis of remnant hyperlipidaemia

Paquette

Bernard

Baass

2022

Current Opinion in Lipidology

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Purpose of reviewIn recent years, there has been interest for the development of simplified diagnosis algorithms of dysbetalipoproteinemia (DBL) in order to avoid the complex testing associated with the Fredrickson criteria (reference method). The purpose of this review is to present recent advances in the field of DBL with a focus on screening and diagnosis.Recent findingsRecently, two different multi-step algorithms for the diagnosis of DBL have been published and their performance has been compared to the Fredrickson criteria. Furthermore, a recent large study demonstrated that only a minority (38%) of DBL patients are carriers of the E2/E2 genotype and that these individuals presented a more severe phenotype.SummaryThe current literature supports the fact that the DBL phenotype is more heterogeneous and complex than previously thought. Indeed, DBL patients can present with either mild or more severe phenotypes that can be distinguished as multifactorial remnant cholesterol disease and genetic apolipoprotein B deficiency. Measurement of apolipoprotein B as well as APOE gene testing are both essential elements in the diagnosis of DBL.

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Adiposity and the development of dyslipidemia in APOE ε2 homozygous subjects: A longitudinal analysis in two population-based cohorts

Cited by 10 publications

References 33 publications

Applicability of Diagnostic Criteria and High Prevalence of Familial Dysbetalipoproteinemia in Russia: A Pilot Study

Applicability of Diagnostic Criteria and High Prevalence of Familial Dysbetalipoproteinemia in Russia: A Pilot Study

Establishing the relationship between familial dysbetalipoproteinemia and genetic variants in theAPOEgene

Diagnosis of remnant hyperlipidaemia

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