Chylomicronemia With a Mutant GPIHBP1 (Q115P) That Cannot Bind Lipoprotein Lipase

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Chylomicronemia with a mutant GPIHBP1 (Q115P) that cannot bind lipoprotein lipase.

OBJECTIVE GPIHBP1 is an endothelial cell protein that binds lipoprotein lipase (LPL) and chylomicrons. Because GPIHBP1 deficiency causes chylomicronemia in mice, we sought to determine whether some cases of chylomicronemia in humans could be attributable to defective GPIHBP1 proteins. METHODS AND RESULTS Patients with severe hypertriglyceridemia (n=60, with plasma triglycerides above the 95th...

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Chylomicronemia with low postheparin lipoprotein lipase levels in the setting of GPIHBP1 defects.

BACKGROUND Recent studies in mice have established that an endothelial cell protein, glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), is essential for the lipolytic processing of triglyceride-rich lipoproteins. METHODS AND RESULTS We report the discovery of a homozygous missense mutation in GPIHBP1 in a young boy with severe chylomicronemia. The muta...

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Autoantibodies against GPIHBP1 as a Cause of Hypertriglyceridemia.

BACKGROUND A protein that is expressed on capillary endothelial cells, called GPIHBP1 (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1), binds lipoprotein lipase and shuttles it to its site of action in the capillary lumen. A deficiency in GPIHBP1 prevents lipoprotein lipase from reaching the capillary lumen. Patients with GPIHBP1 deficiency have low plasma leve...

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Chylomicronemia with Low Postheparin Lipoprotein Lipase Levels in the Setting of GPIHBP1 Defects Franssen; A Key Role for GPIHBP1 in Triglyceride Metabolism in Humans

Background Recent studies in mice have established that an endothelial cell protein, GPIHBP1, is essential for the lipolytic processing of triglyceride-rich lipoproteins. Methods and Results We report the discovery of a homozygous missense mutation in GPIHBP1 in a young boy with severe chylomicronemia. The mutation, p.C65Y, replaces a conserved cysteine in the GPIHBP1’s Ly6 domain with a tyrosi...

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GPIHBP1 missense mutations often cause multimerization of GPIHBP1 and thereby prevent lipoprotein lipase binding.

RATIONALE GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) in the subendothelial spaces and shuttles it to the capillary lumen. GPIHBP1 missense mutations that interfere with LPL binding cause familial chylomicronemia. OBJECTIVE We sought to understand mechanisms by which GPIHBP1 mutations prevent LPL binding and lead to chylomicronemia. METHODS...

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ژورنال

عنوان ژورنال: Arteriosclerosis, Thrombosis, and Vascular Biology

سال: 2009

ISSN: 1079-5642,1524-4636

DOI: 10.1161/atvbaha.109.186577