脂蛋白脂肪酶基因突变导致的家族性乳糜微粒血症患者的早发性动脉粥样硬化。

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

作者信息

Benlian P, De Gennes J L, Foubert L, Zhang H, Gagné S E, Hayden M

机构信息

Department of Medical Genetics, University of British Columbia, Vancouver, Canada.

出版信息

N Engl J Med. 1996 Sep 19;335(12):848-54. doi: 10.1056/NEJM199609193351203.

DOI:10.1056/NEJM199609193351203

PMID:8778602

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, B-mode ultrasonography [corrected], and exercise-tolerance testing after the age of 40. Angiography was performed when indicated. Lipoprotein lipase deficiency was assessed in vivo 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 alleles 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 familiar chylomicronemia as a result of mutations in the lipoprotein lipase gene. Defective lipolysis may increase susceptibility to atherosclerosis in humans.

摘要

背景

脂蛋白脂肪酶缺乏症患者通常在儿童期出现乳糜微粒血症。该综合征一直被认为不具有致动脉粥样硬化性，主要是因为低密度脂蛋白（LDL）胆固醇水平较低。我们对脂蛋白脂肪酶缺乏症患者的动脉粥样硬化情况进行了前瞻性评估。

方法

通过为期14至30年的临床检查，以及在40岁以后进行多普勒超声检查、B型超声检查[校正后]和运动耐量测试，对4例具有家族性乳糜微粒血症表型的患者（2名男性和2名女性）进行颈动脉、外周血管和冠状动脉粥样硬化证据的筛查。在有指征时进行血管造影。通过功能测定和DNA序列分析在体内和体外评估脂蛋白脂肪酶缺乏情况。

结果

所有4例患者均存在脂蛋白脂肪酶严重功能缺陷，由于脂蛋白脂肪酶基因两个等位基因上的错义突变，酶量减少。在所有4例患者中，在55岁之前均观察到外周血管或冠状动脉粥样硬化（或两者皆有）。尽管遵循了脂肪占每日热量摄入10%至15%的低脂饮食，但患者仍有高甘油三酯血症（平均[±标准差]甘油三酯水平为2621±1112mg/dl[29.59±12.55mmol/L]）、血浆高密度脂蛋白胆固醇水平较低（17±7mg/dl[0.43±0.18mmol/L]）以及极低的LDL胆固醇水平（28±16mg/dl[0.72±0.41mmol/L]）。3例患者有一项动脉粥样硬化危险因素，而在1例男性患者中，大量吸烟和糖尿病与疾病的加速进展有关。