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

Anne P BEIGNEUX; Remco FRANSSEN; John J. P KASTELEIN; Loren G FONG; Geesje M DALLINGA-THIE; Stephen G YOUNG; André BENSADOUN; Peter GIN; Kristan MELFORD; Jorge PETER; Rosemary L WALZEM; Michael M WEINSTEIN; Brandon S. J DAVIES; Jan A KUIVENHOVEN

doi:10.1161/ATVBAHA.109.186577

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

Journal article

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

Anne P BEIGNEUX, Remco FRANSSEN, John J. P KASTELEIN, Loren G FONG, Geesje M DALLINGA-THIE, Stephen G YOUNG, André BENSADOUN, Peter GIN, Kristan MELFORD, Jorge PETER, …

Arteriosclerosis, thrombosis, and vascular biology, Vol.29(6), pp.956-962

2009

DOI: 10.1161/ATVBAHA.109.186577

PMCID: PMC2811263

PMID: 19304573

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Abstract

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 percentile for age and gender) were screened for mutations in GPIHBP1. A homozygous GPIHBP1 mutation (c.344A>C) that changed a highly conserved glutamine at residue 115 to a proline (p.Q115P) was identified in a 33-year-old male with lifelong chylomicronemia. The patient had failure-to-thrive as a child but had no history of pancreatitis. He had no mutations in LPL, APOA5, or APOC2. The Q115P substitution did not affect the ability of GPIHBP1 to reach the cell surface. However, unlike wild-type GPIHBP1, GPIHBP1-Q115P lacked the ability to bind LPL or chylomicrons (d < 1.006 g/mL lipoproteins from Gpihbp1(-/-) mice). Mouse GPIHBP1 with the corresponding mutation (Q114P) also could not bind LPL. Conclusions: A homozygous missense mutation in GPIHBP1 (Q115P) was identified in a patient with chylomicronemia. The mutation eliminated the ability of GPIHBP1 to bind LPL and chylomicrons, strongly suggesting that it caused the patient's chylomicronemia.

Fundamental and applied biological sciences. Psychology

Cardiology. Vascular system

General aspects

Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous

Atherosclerosis (general aspects, experimental research)

Biological and medical sciences

Medical sciences

Vertebrates: cardiovascular system

Blood and lymphatic vessels

Details

Title: Subtitle: Chylomicronemia With a Mutant GPIHBP1 (Q115P) That Cannot Bind Lipoprotein Lipase
Creators: Anne P BEIGNEUX - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, United States
Remco FRANSSEN - Department of Vascular Medicine, Amsterdam Medical Center, Netherlands
John J. P KASTELEIN - Department of Vascular Medicine, Amsterdam Medical Center, Netherlands
Loren G FONG - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, United States
Geesje M DALLINGA-THIE - Laboratory of Experimental Vascular Medicine, Amsterdam Medical Center, Netherlands
Stephen G YOUNG - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, United States
André BENSADOUN - Division of Nutritional Science, Cornell University, Ithaca, NY, United States
Peter GIN - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, United States
Kristan MELFORD - Division of Nutritional Science, Cornell University, Ithaca, NY, United States
Jorge PETER - Laboratory of Experimental Vascular Medicine, Amsterdam Medical Center, Netherlands
Rosemary L WALZEM - Departments of Poultry Science and Nutrition and Food Science, Texas A&M University, College Station, United States
Michael M WEINSTEIN - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, United States
Brandon S. J DAVIES - Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, United States
Jan A KUIVENHOVEN - Laboratory of Experimental Vascular Medicine, Amsterdam Medical Center, Netherlands
Resource Type: Journal article
Publication Details: Arteriosclerosis, thrombosis, and vascular biology, Vol.29(6), pp.956-962
DOI: 10.1161/ATVBAHA.109.186577
PMID: 19304573
PMCID: PMC2811263
NLM abbreviation: Arterioscler Thromb Vasc Biol
ISSN: 1079-5642
eISSN: 1524-4636
Publisher: Lippincott Williams & Wilkins; Philadelphia, PA
Language: English
Date published: 2009
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology
Record Identifier: 9984024521402771

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