Russo G T, Meigs J B, Cupples L A, Demissie S, Otvos J D, Wilson P W, Lahoz C, Cucinotta D, Couture P, Mallory T, Schaefer E J, Ordovas J M
Lipid Metabolism Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
Atherosclerosis. 2001 Sep;158(1):173-81. doi: 10.1016/s0021-9150(01)00409-9.
Apolipoprotein (apo) CIII participates in the regulation of the metabolism of triglyceride-rich lipoproteins and it is a major component of chylomicrons and VLDL. The APOC3 gene is on chromosome 11q23 and is highly polymorphic. The less common allele (S2) of the SstI polymorphism on the 3' untranslated region of the APOC3 gene has been previously associated with increased triglycerides, total cholesterol (TC), and apoCIII levels and cardiovascular risk on several, but not all, studies. The aim of this study was to examine the association of this polymorphism with plasma lipid levels, lipoprotein subfractions and coronary heart disease (CHD) risk in a population-based study: The Framingham Offspring Study. The frequency of the S2 allele was 0.086, consistent with previous reports in Caucasian populations. In men, the S2 allele was associated with lower concentrations of high-density lipoprotein cholesterol (HDL-C; P<0.04) and HDL2-C (P<0.02) and a significant increase in apoCIII non-HDL (P<0.05). TG levels were higher in men carriers of the S2 allele, but this association did not reach statistical significance (P=0.30). Conversely, in women, the S2 allele was associated with increased TC (P<0.03), low-density lipoprotein cholesterol (LDL-C; P<0.03), and ApoB levels (P<0.04). Lipoproteins subfractions were also examined using nuclear magnetic resonance (NMR) spectroscopy. S2 male carriers had significantly lower concentrations of large LDL and a significant reduction in LDL particle size (P<0.04). In women, there was a significant increase in intermediate LDL particles (P<0.05) with no significant effect on lipoprotein diameters. We also examined the associations between the S2 allele and biochemical markers of glucose metabolism. In men, the S2 allele was associated with elevated fasting insulin concentrations (P<0.04), whereas no significant associations were observed in women. Despite the described associations with lipid and glucose metabolism related risk factors, we did not find any significant increase in CHD risk associated with the S2 allele in this population.
载脂蛋白（apo）CIII参与富含甘油三酯脂蛋白代谢的调节，是乳糜微粒和极低密度脂蛋白（VLDL）的主要成分。APOC3基因位于11号染色体q23上，具有高度多态性。先前在一些（但并非所有）研究中，APOC3基因3'非翻译区SstI多态性的较罕见等位基因（S2）与甘油三酯、总胆固醇（TC）和apoCIII水平升高以及心血管风险相关。本研究的目的是在一项基于人群的研究——弗雷明汉后代研究中，检验这种多态性与血脂水平、脂蛋白亚组分以及冠心病（CHD）风险之间的关联。S2等位基因的频率为0.086，与先前白种人群的报告一致。在男性中，S2等位基因与高密度脂蛋白胆固醇（HDL-C；P<0.04）和HDL2-C（P<0.02）浓度降低以及apoCIII非HDL显著升高（P<0.05）相关。S2等位基因男性携带者的甘油三酯水平较高，但这种关联未达到统计学显著性（P=0.30）。相反，在女性中，S2等位基因与TC升高（P<0.03）、低密度脂蛋白胆固醇（LDL-C；P<0.03）和载脂蛋白B水平升高（P<0.04）相关。还使用核磁共振（NMR）光谱法检测了脂蛋白亚组分。S2男性携带者的大LDL浓度显著降低，LDL颗粒大小显著减小（P<0.04）。在女性中，中等LDL颗粒显著增加（P<0.05），对脂蛋白直径无显著影响。我们还检验了S2等位基因与葡萄糖代谢生化标志物之间的关联。在男性中，S2等位基因与空腹胰岛素浓度升高相关（P<0.04），而在女性中未观察到显著关联。尽管存在上述与脂质和葡萄糖代谢相关危险因素的关联，但在该人群中，我们未发现S2等位基因与CHD风险有任何显著增加。
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