Garenc Christophe, Couillard Charles, Laflamme Nathalie, Cadelis François, Gagné Claude, Couture Patrick, Julien Pierre, Bergeron Jean
Lipid Research Centre (CRML), CHUL Research Centre, Centre Hospitalier Universitaire de Québec (CHUQ), Sainte-Foy, QC, Canada.
Eur J Hum Genet. 2005 Oct;13(10):1159-65. doi: 10.1038/sj.ejhg.5201469.
Lipoprotein lipase (LPL) plays a major role in triglyceride (TG)-rich lipoprotein catabolism. A mutation at codon 207 (P207L) in the exon 5 of the LPL gene has been associated with 50% reduction in postheparin plasma LPL activity and significant increase in plasma TG levels in heterozygous individuals with low HDL. However, heterogeneity in fasting TG concentrations among these carriers suggests that other factors may be involved in the expression of this hypertriglyceridemic state. Indeed, previous studies have shown that the rare S2 allele of the APOC3 Sst I polymorphism was associated with higher concentrations of TG levels in noncarriers of LPL defect. Therefore, we investigated the association of the APOC3 Sst I variant on fasting lipoprotein-lipid levels in a sample of 35 heterozygous men bearing the LPL P207L mutation. Genetic association analyses were performed using the two-genotype groups S1/S1 and S1/S2. The genotype S1/S2 group was characterized by greater plasma cholesterol (plasma-C, P=0.02), plasma-TG (P=0.04), very low-density lipoproteins (VLDL)-C (P=0.004), VLDL-TG (P=0.01), VLDL-apolipoprotein B (apoB) (P=0.001) levels and cholesterol/HDL-C ratio (P=0.008), as well as lower VLDL-TG/VLDL-apoB ratio compared to the S1/S1 genotype group. These results support an exacerbating effect of the APOC3 Sst I single-nucleotide polymorphism on fasting TG levels since a large number of smaller VLDL particles are observed in LPL-deficient men bearing the APOC3 S2 allele.
脂蛋白脂肪酶（LPL）在富含甘油三酯（TG）的脂蛋白分解代谢中起主要作用。LPL基因外显子5中第207位密码子（P207L）的突变与杂合子个体（高密度脂蛋白水平低）肝素后血浆LPL活性降低50%以及血浆TG水平显著升高有关。然而，这些携带者空腹TG浓度存在异质性，这表明其他因素可能参与了这种高甘油三酯血症状态的表达。事实上，先前的研究表明，APOC3 Sst I多态性的罕见S2等位基因与LPL缺陷非携带者中较高的TG水平有关。因此，我们在35名携带LPL P207L突变的杂合子男性样本中，研究了APOC3 Sst I变体与空腹脂蛋白-脂质水平的关联。使用S1/S1和S1/S2两个基因型组进行遗传关联分析。与S1/S1基因型组相比，S1/S2基因型组的特征是血浆胆固醇（血浆-C，P=0.02）、血浆-TG（P=0.04）、极低密度脂蛋白（VLDL）-C（P=0.004）、VLDL-TG（P=0.01）、VLDL-载脂蛋白B（apoB）（P=0.001）水平以及胆固醇/高密度脂蛋白-C比值（P=0.008）更高，而VLDL-TG/VLDL-apoB比值更低。这些结果支持了APOC3 Sst I单核苷酸多态性对空腹TG水平的加剧作用，因为在携带APOC3 S2等位基因的LPL缺陷男性中观察到大量较小的VLDL颗粒。
