Bijvoet S, Gagné S E, Moorjani S, Gagné C, Henderson H E, Fruchart J C, Dallongeville J, Alaupovic P, Prins M, Kastelein J J, Hayden M R
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
J Lipid Res. 1996 Mar;37(3):640-50.
We have assessed the expression of heterozygosity for lipoprotein lipase (LPL) deficiency by studying a single large French Canadian family comprising 92 persons including 21 carriers of the catalytically defective P207L mutation. Phenotypic changes distinguishing heterozygotes from controls were seen early, before the age of 40 and often before 20 years of age. In the total cohort these changes included an elevation in the mean very low density (VLDL) and intermediate density lipoprotein (IDL) triglyceride (+69%; P = 0.01 and +40%; P = 0.001) and cholesterol (+51%; P = 0.03 and +67%; P = 0.007) and apoB levels but decreased HDL2 and HDL3 cholesterol, (-32%; P = 0.01 and -15%; P = 0.002 respectively). While the lipid compositions of VLDL and IDL were similar between heterozygotes and controls, the low density (LDL) and high density lipoproteins (HDL) of carriers were triglyceride enriched. Heterozygotes also had a markedly lower apoC-III ratio (apoC-III in supernatant/apoC-III in heparin precipitate) (1.46 vs. 3.86 P = 1 x 10(-4)) indicating a substantial enrichment of VLDL and IDL with apoC-III and depletion of HDL apoC-III supporting this ratio as an effective index for efficiency of lipolysis. LpA-I was markedly reduced (0.34 vs. 0.43 P = 1 x 10(-5)) showing that levels of this particle are partly dependent on LPL catalytic activity. Heterozygotes manifest from an early age with a markedly reduced HDL, LpA-I, apoC-III ratio and an increased TC/HDLc ratio which would predict a relatively increased risk of premature coronary artery disease, compared to their normal siblings.
我们通过研究一个由92人组成的法裔加拿大家庭来评估脂蛋白脂肪酶（LPL）缺乏杂合子的表达情况，该家庭中有21名携带催化缺陷型P207L突变的携带者。区分杂合子与对照组的表型变化在40岁之前就已出现，且常在20岁之前。在整个队列中，这些变化包括极低密度脂蛋白（VLDL）和中间密度脂蛋白（IDL）甘油三酯均值升高（分别升高69%；P = 0.01和40%；P = 0.001）以及胆固醇升高（分别升高51%；P = 0.03和67%；P = 0.007）和载脂蛋白B水平升高，但HDL2和HDL3胆固醇降低（分别降低32%；P = 0.01和15%；P = 0.002）。虽然杂合子与对照组之间VLDL和IDL的脂质组成相似，但携带者的低密度脂蛋白（LDL）和高密度脂蛋白（HDL）富含甘油三酯。杂合子的载脂蛋白C-III比值（上清液中的载脂蛋白C-III/肝素沉淀中的载脂蛋白C-III）也显著降低（1.46对3.86，P = 1×10⁻⁴），表明VLDL和IDL中载脂蛋白C-III大量富集，而HDL载脂蛋白C-III减少，支持该比值作为脂解效率的有效指标。载脂蛋白A-I显著降低（0.34对0.43，P = 1×10⁻⁵），表明该颗粒水平部分依赖于LPL催化活性。与正常的兄弟姐妹相比，杂合子在早年就表现出HDL、载脂蛋白A-I、载脂蛋白C-III比值显著降低，以及TC/HDLc比值升高，这预示着过早患冠状动脉疾病的风险相对增加。
