Premature atherosclerosis in patients with familial chylomicronemia caused by mutations in the lipoprotein lipase gene

Pascale Benlian, Jean Luc De Gennes, Luc Foubert, Hanfang Zhang, S. Eric Gagné, Michael Hayden

Research output: Contribution to journalArticle

249 Citations (Scopus)

Abstract

Background: Patients with lipoprotein lipase deficiency usually present with chylomicronemia in childhood. The syndrome has been considered nonatherogenic primarily because of the low levels of low-density lipoprotein (LDL) cholesterol. We prospectively evaluated patients with lipoprotein lipase deficiency for atherosclerosis. Methods: Evidence of carotid, peripheral, and coronary atherosclerosis was sought in four patients (two men and two women) with the phenotype of familial chylomicronemia by clinical examination over a period of 14 to 30 years and by Doppler ultrasonography, ultrasonography, and exercise-tolerance testing after the age of 40. Angiography was performed when indicated. Lipoprotein lipase deficiency was assessed in viva and in vitro by functional assays and DNA-sequence analysis. Results: All four patients had a profound functional deficiency of lipoprotein lipase with a reduced enzymatic mass due to missense mutations on both allales of the lipoprotein lipase gene. In all four patients, peripheral or coronary atherosclerosis (or both) was observed before the age of 55. Despite following a low-fat diet in which fat composed 10 to 15 percent of the daily caloric intake, the patients had hypertriglyceridemia (mean [±SD] triglyceride level, 2621±1112 mg per deciliter [29.59±12.55 mmol per liter]), low plasma levels of high-density lipoprotein cholesterol (17±7 mg per deciliter [0.43±0.18 mmol per liter]), and very low levels of LDL cholesterol (28±16 mg per deciliter [0.72±0.41 mmol per liter]). Three patients had one risk factor for atherosclerosis, whereas in one male patient, heavy smoking and diabetes were associated with an accelerated course of the disease. Conclusions: Premature atherosclerosis can occur in patients with familial chylomicronemia as a result of mutations in the lipoprotein lipase gene. Defective lipolysis may increase susceptibility to atherosclerosis in humans.

Original languageEnglish (US)
Pages (from-to)848-854
Number of pages7
JournalNew England Journal of Medicine
Volume335
Issue number12
DOIs
StatePublished - Sep 19 1996

Fingerprint

Hyperlipoproteinemia Type I
Lipoprotein Lipase
Atherosclerosis
Mutation
Genes
LDL Cholesterol
Coronary Artery Disease
Doppler Ultrasonography
Fat-Restricted Diet
Carotid Artery Diseases
Exercise Tolerance
Hypertriglyceridemia
Lipolysis
Missense Mutation
Energy Intake
DNA Sequence Analysis
HDL Cholesterol
Ultrasonography
Angiography
Triglycerides

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Premature atherosclerosis in patients with familial chylomicronemia caused by mutations in the lipoprotein lipase gene. / Benlian, Pascale; De Gennes, Jean Luc; Foubert, Luc; Zhang, Hanfang; Gagné, S. Eric; Hayden, Michael.

In: New England Journal of Medicine, Vol. 335, No. 12, 19.09.1996, p. 848-854.

Research output: Contribution to journalArticle

Benlian, Pascale ; De Gennes, Jean Luc ; Foubert, Luc ; Zhang, Hanfang ; Gagné, S. Eric ; Hayden, Michael. / Premature atherosclerosis in patients with familial chylomicronemia caused by mutations in the lipoprotein lipase gene. In: New England Journal of Medicine. 1996 ; Vol. 335, No. 12. pp. 848-854.
@article{6b810c8835b94046abcca5203ae41607,
title = "Premature atherosclerosis in patients with familial chylomicronemia caused by mutations in the lipoprotein lipase gene",
abstract = "Background: Patients with lipoprotein lipase deficiency usually present with chylomicronemia in childhood. The syndrome has been considered nonatherogenic primarily because of the low levels of low-density lipoprotein (LDL) cholesterol. We prospectively evaluated patients with lipoprotein lipase deficiency for atherosclerosis. Methods: Evidence of carotid, peripheral, and coronary atherosclerosis was sought in four patients (two men and two women) with the phenotype of familial chylomicronemia by clinical examination over a period of 14 to 30 years and by Doppler ultrasonography, ultrasonography, and exercise-tolerance testing after the age of 40. Angiography was performed when indicated. Lipoprotein lipase deficiency was assessed in viva and in vitro by functional assays and DNA-sequence analysis. Results: All four patients had a profound functional deficiency of lipoprotein lipase with a reduced enzymatic mass due to missense mutations on both allales of the lipoprotein lipase gene. In all four patients, peripheral or coronary atherosclerosis (or both) was observed before the age of 55. Despite following a low-fat diet in which fat composed 10 to 15 percent of the daily caloric intake, the patients had hypertriglyceridemia (mean [±SD] triglyceride level, 2621±1112 mg per deciliter [29.59±12.55 mmol per liter]), low plasma levels of high-density lipoprotein cholesterol (17±7 mg per deciliter [0.43±0.18 mmol per liter]), and very low levels of LDL cholesterol (28±16 mg per deciliter [0.72±0.41 mmol per liter]). Three patients had one risk factor for atherosclerosis, whereas in one male patient, heavy smoking and diabetes were associated with an accelerated course of the disease. Conclusions: Premature atherosclerosis can occur in patients with familial chylomicronemia as a result of mutations in the lipoprotein lipase gene. Defective lipolysis may increase susceptibility to atherosclerosis in humans.",
author = "Pascale Benlian and {De Gennes}, {Jean Luc} and Luc Foubert and Hanfang Zhang and Gagn{\'e}, {S. Eric} and Michael Hayden",
year = "1996",
month = "9",
day = "19",
doi = "10.1056/NEJM199609193351203",
language = "English (US)",
volume = "335",
pages = "848--854",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "12",

}

TY - JOUR

T1 - Premature atherosclerosis in patients with familial chylomicronemia caused by mutations in the lipoprotein lipase gene

AU - Benlian, Pascale

AU - De Gennes, Jean Luc

AU - Foubert, Luc

AU - Zhang, Hanfang

AU - Gagné, S. Eric

AU - Hayden, Michael

PY - 1996/9/19

Y1 - 1996/9/19

N2 - Background: Patients with lipoprotein lipase deficiency usually present with chylomicronemia in childhood. The syndrome has been considered nonatherogenic primarily because of the low levels of low-density lipoprotein (LDL) cholesterol. We prospectively evaluated patients with lipoprotein lipase deficiency for atherosclerosis. Methods: Evidence of carotid, peripheral, and coronary atherosclerosis was sought in four patients (two men and two women) with the phenotype of familial chylomicronemia by clinical examination over a period of 14 to 30 years and by Doppler ultrasonography, ultrasonography, and exercise-tolerance testing after the age of 40. Angiography was performed when indicated. Lipoprotein lipase deficiency was assessed in viva and in vitro by functional assays and DNA-sequence analysis. Results: All four patients had a profound functional deficiency of lipoprotein lipase with a reduced enzymatic mass due to missense mutations on both allales of the lipoprotein lipase gene. In all four patients, peripheral or coronary atherosclerosis (or both) was observed before the age of 55. Despite following a low-fat diet in which fat composed 10 to 15 percent of the daily caloric intake, the patients had hypertriglyceridemia (mean [±SD] triglyceride level, 2621±1112 mg per deciliter [29.59±12.55 mmol per liter]), low plasma levels of high-density lipoprotein cholesterol (17±7 mg per deciliter [0.43±0.18 mmol per liter]), and very low levels of LDL cholesterol (28±16 mg per deciliter [0.72±0.41 mmol per liter]). Three patients had one risk factor for atherosclerosis, whereas in one male patient, heavy smoking and diabetes were associated with an accelerated course of the disease. Conclusions: Premature atherosclerosis can occur in patients with familial chylomicronemia as a result of mutations in the lipoprotein lipase gene. Defective lipolysis may increase susceptibility to atherosclerosis in humans.

AB - Background: Patients with lipoprotein lipase deficiency usually present with chylomicronemia in childhood. The syndrome has been considered nonatherogenic primarily because of the low levels of low-density lipoprotein (LDL) cholesterol. We prospectively evaluated patients with lipoprotein lipase deficiency for atherosclerosis. Methods: Evidence of carotid, peripheral, and coronary atherosclerosis was sought in four patients (two men and two women) with the phenotype of familial chylomicronemia by clinical examination over a period of 14 to 30 years and by Doppler ultrasonography, ultrasonography, and exercise-tolerance testing after the age of 40. Angiography was performed when indicated. Lipoprotein lipase deficiency was assessed in viva and in vitro by functional assays and DNA-sequence analysis. Results: All four patients had a profound functional deficiency of lipoprotein lipase with a reduced enzymatic mass due to missense mutations on both allales of the lipoprotein lipase gene. In all four patients, peripheral or coronary atherosclerosis (or both) was observed before the age of 55. Despite following a low-fat diet in which fat composed 10 to 15 percent of the daily caloric intake, the patients had hypertriglyceridemia (mean [±SD] triglyceride level, 2621±1112 mg per deciliter [29.59±12.55 mmol per liter]), low plasma levels of high-density lipoprotein cholesterol (17±7 mg per deciliter [0.43±0.18 mmol per liter]), and very low levels of LDL cholesterol (28±16 mg per deciliter [0.72±0.41 mmol per liter]). Three patients had one risk factor for atherosclerosis, whereas in one male patient, heavy smoking and diabetes were associated with an accelerated course of the disease. Conclusions: Premature atherosclerosis can occur in patients with familial chylomicronemia as a result of mutations in the lipoprotein lipase gene. Defective lipolysis may increase susceptibility to atherosclerosis in humans.

UR - http://www.scopus.com/inward/record.url?scp=0029808302&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029808302&partnerID=8YFLogxK

U2 - 10.1056/NEJM199609193351203

DO - 10.1056/NEJM199609193351203

M3 - Article

C2 - 8778602

AN - SCOPUS:0029808302

VL - 335

SP - 848

EP - 854

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 12

ER -