No evidence of accelerated atherosclerosis in a 66-yr-old chylomicronemia patient homozygous for the nonsense mutation (Tyr61→Stop) in the lipoprotein lipase gene

Ebara, Tetsu; Okubo, Minoru; Horinishi, Asako; Adachi, Mitsuru; Hirano, Tsutomu

doi:10.1016/s0021-9150(01)00510-x

Cited by 30 publications

(22 citation statements)

References 20 publications

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“…There have also been reports of the frequent occurrence in heterozygotes of familial combined hyperlipidemia (FCHL) 12) and monogenic familial hypertriglyceridemia 16) , which are common hyperlipidemia related to atherosclerosis; however, it remains controversial whether homozygotes with LPL gene abnormality are likely to develop atherosclerosis. A Canadian group that followed-up 4 patients with LPL deficiency over 14-30 years reported that coronary angiography established atherosclerotic lesions in all patients before the age of 55 years 18) , but studies on homozygotes in Japan 19,20) both reported no advanced atherosclerotic lesion in those Japanese patients.…”

Section: C) Clinical Symptomsmentioning

confidence: 99%

Diagnosis and Management of Type I and Type V Hyperlipoproteinemia

Gotoda

Shirai

Ohta

et al. 2012

JAT

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Both type and type hyperlipoproteinemia are characterized by severe hypertriglyceridemia due to an increase in chylomicrons. Type hyperlipoproteinemia is caused by a decisive abnormality of the lipoprotein lipase (LPL)-apolipoprotein C-system, whereas the cause of type hyperlipoproteinemia is more complicated and more closely related to acquired environmental factors. Since the relationship of hypertriglyceridemia with atherosclerosis is not as clear as that of hypercholesterolemia, and since type and hyperlipoproteinemia are relatively rare, few guidelines for their diagnosis and treatment have been established; however, type and hyperlipoproteinemia are clinically important as underlying disorders of acute pancreatitis, and appropriate management is necessary to prevent or treat such complications. Against such a background, here we propose guidelines primarily concerning the diagnosis and management of type and hyperlipoproteinemia in Japanese.

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Section: C) Clinical Symptomsmentioning

confidence: 99%

Diagnosis and Management of Type I and Type V Hyperlipoproteinemia

Gotoda

Shirai

Ohta

et al. 2012

JAT

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“…Two subjects had chylomicronemia due to lipoprotein lipase deficiency, and their fasting serum triglyceride levels were Ͼ 1,000 mg/dl. We have reported the analysis of the lipoprotein lipase gene in one of these patients (11).…”

Section: Subjectsmentioning

confidence: 99%

A novel and simple method for quantification of small, dense LDL

Hirano

Ito

Saegusa

et al. 2003

Journal of Lipid Research

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184

159

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A preponderance of small, dense (sd) LDL is strongly associated with the development of coronary heart disease, but the method for the measurement of sd LDL is too laborious for clinical use. We report a simple method for the quantification of sd LDL that is applicable to an autoanalyzer. This method consists of two steps: first, to precipitate the lipoprotein of density (d) Ͻ 1.044 g/ml using heparin-magnesium; and second, to measure LDL-cholesterol in the supernatant by the homogenous method or apolipoprotein B (apoB) by an immunoturbidometric assay. LDL particles are heterogenous with respect to size and density (d) of lipid composition. Two distinct phenotypes based on LDL particles have been recognized: pattern A, with a higher proportion of large, buoyant LDL particles, and pattern B, with a predominance of small, dense (sd) LDL particles (1, 2, 3). It has been suggested that compared with buoyant LDL, sd LDLs are highly atherogenic as a result of their higher penetration into the arterial wall, their lower binding affinity for the LDL receptor, prolonged plasma half-life, and lower resistance to oxidative stress (4, 5). Several studies have reported a 2-to 3-fold increase in coronary heart disease (CHD) risk among patients with pattern B (1, 2). We have also reported that sd LDL is highly associated with CHD events in Japanese, an ethnic group with lower LDL-cholesterol levels, compared with Western populations (6, 7). Therefore, sd LDL has been highlighted as a new potent risk marker for CHD.LDL particle size is usually measured by gradient gel electrophoresis (GGE) using nondenaturing polyacrylamide according to the method of Krauss and Burke (8). However, this procedure requires a long assay time, i.e., overnight electrophoresis, staining, and destaining. Of course, this assay does not allow quantitative determination of sd LDL. Ultracentrifugation is the standard technique for the isolation of the sd LDL fraction (9, 10) and allows quantification of sd LDL. Griffin et al. (10) reported that LDL-III (equivalent to sd LDL, with d ϭ 1.044-1.060 g/ml) concentration was significantly increased in CHD patients, and the relative CHD risk was increased 4.5-fold in individuals having LDL-III concentrations (protein plus lipid) Ͼ 100 mg/dl, compared with those with lower concentrations. Their study suggests that in addition to measurement of LDL size, quantification of sd LDL is also useful for the assessment of CHD risk. However, the ultracentrifugation technique is too laborious for general clinical use, because it requires special equipment and a long running time.It is well known that a combination of divalent cations and polyanions precipitates apolipoprotein B (apoB)-containing lipoproteins, which allows for the measurement of HDL-cholesterol. However, we found that the combination of heparin and Mg did not precipitate all of the apoBcontaining lipoproteins; the denser part of LDL remained in the supernatant. Here we report a simple precipitation method for the direct measurement of sd LDL in serum

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“…It has been proposed that LPL protein lacking any lipase activity may function as a bridge between apoB-containing lipoproteins and proteoglycans on vessel walls, thereby retaining atherogenic lipoproteins on endothelial cells, and leading to the progression of atherosclerosis (7,14). In fact, patients with complete LPL deficiency, whereby both enzymatic activity and protein mass are absent, reportedly exhibit a nonatherogenic phenotype (15,16), while patients with missense mutations which result in the absence of LPL activity with retention of the LPL protein are prone to atherogenesis (4,(6)(7)(8). Therefore, functionally inactive R243H-LPL protein may have played a role in the development of the severe atherosclerosis observed in this patient.…”

Section: Discussionmentioning

confidence: 84%

Lipoprotein Lipase Deficiency (R243H) in a Type 2 Diabetes Patient with Multiple Arterial Aneurysms

et al. 2016

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Lipoprotein lipase (LPL) deficiency is a rare monogenic disorder that manifests as severe hypertriglyceridemia. Whether or not LPL deficiency accelerates the development of atherosclerosis remains controversial. We herein report a 66-year-old woman who was homozygous for the R243H LPL mutation. She had developed multiple arterial aneurysms and systemic atherosclerosis despite good control of other atherogenic risk factors, including diabetes. Furthermore, although intensive pharmaceutical therapies had been minimally effective, medium chain triglyceride (MCT) therapy reduced the serum triglyceride levels. Thus, this case suggests important role that mutated LPL protein plays in the progression of atherosclerosis and that MCT therapy is potentially effective, even for severe hypertriglyceridemia due to LPL deficiency.

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No evidence of accelerated atherosclerosis in a 66-yr-old chylomicronemia patient homozygous for the nonsense mutation (Tyr61→Stop) in the lipoprotein lipase gene

Cited by 30 publications

References 20 publications

Diagnosis and Management of Type I and Type V Hyperlipoproteinemia

Diagnosis and Management of Type I and Type V Hyperlipoproteinemia

A novel and simple method for quantification of small, dense LDL

Lipoprotein Lipase Deficiency (R243H) in a Type 2 Diabetes Patient with Multiple Arterial Aneurysms

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