Missense mutation Leu72Pro located on the carboxyl terminal amphipathic helix of apolipoprotein C-II causes familial chylomicronemia syndrome

Lam, Ching‐Wan; Yuen, Yuet-Ping; Cheng, Anna Wai-Fun; Chan, Yan-Wo; Tong, Sui-Fan

doi:10.1016/j.cca.2005.07.025

Cited by 24 publications

(6 citation statements)

References 15 publications

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“…120 Indeed, several case reports indicate chylomicronaemia and decreased concentrations of apoCII in individuals with APOC2 loss-of-function mutations. 121–125 However, so far, these numbers are too small for full observational studies, and MRTs have not yet been conducted. In 38 patients with very premature STEMI, 4 patients with low apoCII concentrations (≤5.0 mg/L) had worse reinfarction-free or revascularization-free survival than those with apoCII >5.0 mg/L during follow-up of 10 years (Figure 5(a) and (b)).…”

Section: Genetic Evidence For the Role Of Apolipoproteins In Cvdmentioning

confidence: 99%

Apolipoprotein profiling as a personalized approach to the diagnosis and treatment of dyslipidaemia

2019

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An elevated low-density lipoprotein cholesterol concentration is a classical risk factor for cardiovascular disease. This has led to pharmacotherapy in patients with atherosclerotic heart disease or high heart disease risk with statins to reduce serum low-density lipoprotein cholesterol. Even in patients in whom the target levels of low-density lipoprotein cholesterol are reached, there remains a significant residual cardiovascular risk; this is due, in part, to a focus on low-density lipoprotein cholesterol alone and neglect of other important aspects of lipoprotein metabolism. A more refined lipoprotein analysis will provide additional information on the accumulation of very low-density lipoproteins, intermediate density lipoproteins, chylomicrons, chylomicron-remnants and Lp(a) concentrations. Instead of measuring the cholesterol and triglyceride content of the lipoproteins, measurement of their apolipoproteins (apos) is more informative. Apos are either specific for a particular lipoprotein or for a group of lipoproteins. In particular measurement of apos in atherogenic particles is more biologically meaningful than the measurement of the cholesterol concentration contained in these particles. Applying apo profiling will not only improve characterization of the lipoprotein abnormality, but will also improve definition of therapeutic targets. Apo profiling aligns with the concept of precision medicine by which an individual patient is not treated as ‘average’ patient by the average (dose of) therapy. This concept of precision medicine fits the unmet clinical need for stratified cardiovascular medicine. The requirements for clinical application of proteomics, including apo profiling, can now be met using robust mass spectrometry technology which offers desirable analytical performance and standardization.

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Section: Genetic Evidence For the Role Of Apolipoproteins In Cvdmentioning

confidence: 99%

Apolipoprotein profiling as a personalized approach to the diagnosis and treatment of dyslipidaemia

2019

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“…Some of the missense mutations impair binding of apo-CII to TRLs and are associated with extremely low levels of apo-CII in the plasma. One of the missense mutations, Leu72Pro, underscored the importance of apo-CII's C terminus in LPL activation (Lam et al 2006). The diagnosis of apo-CII deficiency can be suspected when low LPL activity levels in the postheparin plasma are normalized with apo-CII-containing plasma (Breckenridge et al 1978).…”

Section: Apo-cii Deficiencymentioning

confidence: 99%

Biochemistry and pathophysiology of intravascular and intracellular lipolysis

2013

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All organisms use fatty acids (FAs) for energy substrates and as precursors for membrane and signaling lipids. The most efficient way to transport and store FAs is in the form of triglycerides (TGs); however, TGs are not capable of traversing biological membranes and therefore need to be cleaved by TG hydrolases (“lipases”) before moving in or out of cells. This biochemical process is generally called “lipolysis.” Intravascular lipolysis degrades lipoprotein-associated TGs to FAs for their subsequent uptake by parenchymal cells, whereas intracellular lipolysis generates FAs and glycerol for their release (in the case of white adipose tissue) or use by cells (in the case of other tissues). Although the importance of lipolysis has been recognized for decades, many of the key proteins involved in lipolysis have been uncovered only recently. Important new developments include the discovery of glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), the molecule that moves lipoprotein lipase from the interstitial spaces to the capillary lumen, and the discovery of adipose triglyceride lipase (ATGL) and comparative gene identification-58 (CGI-58) as crucial molecules in the hydrolysis of TGs within cells. This review summarizes current views of lipolysis and highlights the relevance of this process to human disease.

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“…Most patients were white (80.3%), and the mean body mass index (BMI) was 25.0 6 5.7 kg/m 2 (mean 6 SD), although BMI varied widely between 14.9 and 46.6 kg/m 2 ( Table 1). Age at time of FCS diagnosis was available for 46 patients and ranged from 0 to 75 years (median [P25, P75] 5 27 [15,41] years) as shown in Figure 3. FCS was diagnosed before the age of 20 years in 14/46 patients (30.4%), with 6 patients (13.0%) being diagnosed before the age of 5 years.…”

Section: Resultsmentioning

confidence: 99%

“…[8][9][10][11][12][13] Apolipoprotein C-II is an essential activator of LPL and bi-allelic mutations in the APOC2 gene leads to functional LPL deficiency and phenotypic FCS. 5,[14][15][16] Apolipoprotein A-V also enhances the activity of LPL, and rare mutations in the APOA5 gene have been described as causing FCS, although penetrance is often incomplete and hypertriglyceridemia may be noted only later in life. [17][18][19] Besides LPL gene mutations, mutations in genes involved in cellular processing and/or endothelial binding of LPL can also cause FCS.…”

Section: Introductionmentioning

confidence: 99%

Characterizing familial chylomicronemia syndrome: Baseline data of the APPROACH study

Blom

O’Dea

Digenio

et al. 2018

Journal of Clinical Lipidology

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Missense mutation Leu72Pro located on the carboxyl terminal amphipathic helix of apolipoprotein C-II causes familial chylomicronemia syndrome

Cited by 24 publications

References 15 publications

Apolipoprotein profiling as a personalized approach to the diagnosis and treatment of dyslipidaemia

Apolipoprotein profiling as a personalized approach to the diagnosis and treatment of dyslipidaemia

Biochemistry and pathophysiology of intravascular and intracellular lipolysis

Characterizing familial chylomicronemia syndrome: Baseline data of the APPROACH study

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