Hegele Robert A
Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Curr Opin Lipidol. 2025 Apr 1;36(2):96-103. doi: 10.1097/MOL.0000000000000974. Epub 2025 Jan 15.
Genetic testing of patients with severe hypertriglyceridemia often identifies a single heterozygous pathogenic variant in the LPL gene. The complex and variable phenotype associated with this genotype is the topic of this review.
Previous research showed that heterozygosity for lipoprotein lipase deficiency is associated with reduced but variable post heparin lipolytic activity alongside inconsistent plasma lipid phenotypes ranging from normal to mild-to-moderate to severe hypertriglyceridemia. Recent research confirms and extends these observations, showing that a heterozygous individual can express a highly variable phenotype over time, depending on the presence of secondary factors. About 10% (range 8-20%) of patients with severe hypertriglyceridemia or multifactorial chylomicronemia syndrome are heterozygous for a rare pathogenic LPL variant, and a clinically relevant minority of these has recalcitrant or sustained hypertriglyceridemia.
Heterozygosity for lipoprotein lipase deficiency predisposes to hypertriglyceridemia, which is sometimes severe depending on secondary factors, but is typically quite responsive to routine interventions such as diet, lifestyle and existing lipid-lowering therapies. However, many heterozygotes for pathogenic variants in LPL have completely normal plasma lipids.
对重度高甘油三酯血症患者进行基因检测时，常可在脂蛋白脂肪酶（LPL）基因中发现单个杂合致病性变异。本文综述的主题是与该基因型相关的复杂且多变的表型。
既往研究表明，脂蛋白脂肪酶缺乏症的杂合性与肝素后脂解活性降低但存在变异有关，同时血浆脂质表型也不一致，范围从正常到轻度至中度再到重度高甘油三酯血症。近期研究证实并扩展了这些观察结果，表明杂合个体随时间推移可表现出高度可变的表型，这取决于次要因素的存在。约10%（范围8%-20%）的重度高甘油三酯血症或多因素乳糜微粒血症综合征患者为罕见致病性LPL变异的杂合子，其中临床上有一部分患者存在顽固性或持续性高甘油三酯血症。
脂蛋白脂肪酶缺乏症的杂合性易导致高甘油三酯血症，其严重程度有时取决于次要因素，但通常对饮食、生活方式和现有降脂治疗等常规干预措施反应良好。然而，许多LPL致病性变异的杂合子血浆脂质完全正常。
