Chylomicronemia With a Mutant GPIHBP1 (Q115P) That Cannot Bind Lipoprotein Lipase
作者： Anne P. Beigneux , Remco Franssen , André Bensadoun , Peter Gin , Kristan Melford
DOI: 10.1161/ATVBAHA.109.186577
关键词:
摘要: Objective— GPIHBP1 is an endothelial cell protein that binds lipoprotein lipase (LPL) and chylomicrons. Because deficiency causes chylomicronemia in mice, we sought to determine whether some cases of humans could be attributable defective proteins. Methods Results— Patients with severe hypertriglyceridemia (n=60, plasma triglycerides above the 95th percentile for age gender) were screened mutations GPIHBP1. A homozygous mutation (c.344A>C) changed a highly conserved glutamine at residue 115 proline (p.Q115P) was identified 33-year-old male lifelong chylomicronemia. The patient had failure-to-thrive as child but no history pancreatitis. He LPL, APOA5, or APOC2. Q115P substitution did not affect ability reach surface. However, unlike wild-type GPIHBP1, GPIHBP1-Q115P lacked bind LPL chylomicrons (d < 1.006 g/mL lipoproteins from Gpihbp1−/− mice). ...
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