A novel sequence variant in APOA5 gene found in patients with severe hypertriglyceridemia

Oliva, Claudio Priore; Pisciotta, Livia; Guardamagna, Ornella; Bellocchio, Antonella; Tarugi, Patrizia; Schaap, Frank G.; Calandra, Sebastiano

doi:10.1016/j.atherosclerosis.2006.04.010

Cited by 39 publications

(13 citation statements)

References 13 publications

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“…One example in support of this hypothesis is the finding that adjustment for apoC-III, a negative regulator of LPL hydrolysis, attenuates the positive association of apoA-V levels with TG levels in hypertriglyceridemic patients (F. G. Schaap, unpublished results). This hypothesis is further supported by studies showing that the clinical manifestation of severe dyslipidemia among carriers of an APOA5-truncating mutation is entirely dependent on additional effects mediated by the second common TG-increasing allele or on other factors such as age, glucose levels, and obesity (19)(20)(21). Furthermore, the remaining masked etiology of severe hypertriglyceridemia after exclusion of known TG-modulating factors in the majority of patients diagnosed with this disorder suggests that additional modulators of TG metabolism remain unidentified.…”

Section: Apoa-v Serum Level and Tgsmentioning

confidence: 83%

“…Carriers of the two single nucleotide polymorphisms (SNPs) representing these haplotypes, 21131T.C for APOA5*2 and c.56C.G (S19W) for APOA5*3, have consistently been described to present with higher plasma TG levels and an atherogenic lipid profile (e.g., increased levels of small, dense LDLs) (15)(16)(17)(18). Further support that apoA-V plays an important role in human TG metabolism comes from individuals with point mutations in the APOA5 gene, resulting in premature truncation of the apoA-V protein, who develop severe hypertriglyceridemia and/or hyperchylomicronemia (19)(20)(21).…”

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confidence: 99%

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Apolipoprotein A-V, triglycerides and risk of coronary artery disease: the prospective Epic-Norfolk Population Study

Vaessen

Schaap

Kuivenhoven

et al. 2006

Journal of Lipid Research

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In mouse models, apolipoprotein A-V (apoA-V) exhibits triglyceride (TG)-lowering effects. We investigated the apoA-V/TG relationship and the association of apoA-V with coronary artery disease (CAD) risk by determining serum apoA-V levels and genotypes in a nested case-control (n 5 1,034/2,031) study. Both univariate and multivariate apoA-V levels showed no association with future CAD (P 5 0.4 and 0.5, respectively). Unexpectedly, there was a significant positive correlation between serum apoA-V and TG in men and women (r 5 0.36 and 0.28, respectively, P , 0.001 each) but a negative correlation between apoA-V and LPL mass (r 5 20.14 and 20.12 for men and women respectively, P , 0.001 each). The frequency of the c.56C.G polymorphism did not differ between cases and controls despite significant positive association of c.56G with both apoA-V and TG levels. For 21131T.C, the minor allele was significantly associated with lower apoA-V yet higher TG levels and was overrepresented in cases (P 5 0.047). The association of 21131T.C with CAD risk, however, was independent of apoA-V levels and likely acts through linkage disequilibrium with APOC3 variants. The positive correlation of apoA-V levels with TG levels, negative correlation with LPL levels, and lack of association with CAD risk highlight the need for further human studies to clarify the role of apoA-V.-Vaessen, S.

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Section: Apoa-v Serum Level and Tgsmentioning

confidence: 83%

mentioning

confidence: 99%

Apolipoprotein A-V, triglycerides and risk of coronary artery disease: the prospective Epic-Norfolk Population Study

Vaessen

Schaap

Kuivenhoven

et al. 2006

Journal of Lipid Research

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“…pregnancy, age and obesity, lead to massive elevation of plasma TG levels in man [Oliva et al, 2004;Marcais et al, 2005;Oliva et al, 2006]. Although not directly aimed at developing a therapy, several investigators have shown that adenoviral vectors can be successfully used to induce overexpression of apoAV which is naturally expressed in the liver.…”

Section: Apoav Over-expressionmentioning

confidence: 99%

Gene Therapy in Disorders of Lipoprotein Metabolism

Vaessen

Twisk²,

Kastelein³

et al. 2007

CGT

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Current pharmacologic interventions in lipid metabolism are insufficient in a subset of patients at increased risk of cardiovascular disease. In particular, several monogenetic disorders of lipid metabolism with diverse clinical complications are beyond treatment to date. Somatic gene transfer is a potential approach to treat these disorders. This review describes the efforts made thus far to develop gene therapy for 3 major classes of dyslipidemia: Increased levels of low-density lipoprotein cholesterol, reduced levels of high-density lipoprotein cholesterol and increased plasma triglyceride levels. For many of the genetic causes underlying these conditions, proof-of-principle studies have been performed and in combination with improved vectors some of these strategies may be feasible for clinical use in the future.

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“…Accordingly, the Apoa5 mouse knock-out demonstrates an inverse relationship between gene expression and plasma TG [2]. In humans there are rare mutations in APOA5 (such as Q148X, Q139X) [19,20] causing a premature truncation of the protein associated with Type I and V lipoprotein phenotypes or familial hypertriglyceridemia. These disorders are mainly characterized by plasma accumulation of triglyceride-rich particles, chylomicrons alone or chylomicrons and VLDL, both in the fasting and postprandial state.…”

Section: Introductionmentioning

confidence: 99%

Tissue-specific DNA methylation profiles regulate liver-specific expression of the APOA1/C3/A4/A5 cluster and can be manipulated with demethylating agents on intestinal cells

et al. 2014

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A novel sequence variant in APOA5 gene found in patients with severe hypertriglyceridemia

Cited by 39 publications

References 13 publications

Apolipoprotein A-V, triglycerides and risk of coronary artery disease: the prospective Epic-Norfolk Population Study

Apolipoprotein A-V, triglycerides and risk of coronary artery disease: the prospective Epic-Norfolk Population Study

Gene Therapy in Disorders of Lipoprotein Metabolism

Tissue-specific DNA methylation profiles regulate liver-specific expression of the APOA1/C3/A4/A5 cluster and can be manipulated with demethylating agents on intestinal cells

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