Talmud Philippa J, Martin Steve, Taskinen Marja-Riitta, Frick M Heikki, Nieminen Markku S, Kesäniemi Y Antero, Pasternack Amos, Humphries Steve E, Syvänne Mikko
Centre for Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Royal Free and University College Medical School, London, UK.
J Lipid Res. 2004 Apr;45(4):750-6. doi: 10.1194/jlr.M300458-JLR200. Epub 2004 Jan 16.
Animal and human studies support a role for apolipoprotein A-V (apoA-V) in triglyceride (TG) metabolism. We examined the relationship of APOA5 -1131T>C and S19W with lipid subfractions and progression of atherosclerosis in the Lopid Coronary Angiography Trial. Compared with -1131TT men (n = 242), carriers of the -1131C allele (n = 54) had significantly higher total TG (P = 0.03), reflected in significantly increased VLDL mass [higher VLDL-TG, VLDL-cholesterol, VLDL-protein, and surface lipids (all P < 0.05)]. Because apoB levels were unaffected by genotype, this suggests an increase in VLDL size and not number. Compared with 19SS men (n = 268), 19W carriers (n = 44) had higher intermediate density lipoprotein (IDL)-TG, IDL-cholesterol (P = 0.04), and IDL-surface components [free cholesterol (P = 0.005) and phospholipids (P = 0.017)] but not protein content, suggesting an increase in IDL lipid enrichment resulting in an increase in IDL size. 19W carriers also showed a trend toward increased progression of atherogenesis, as measured by change in average diameter of segments (-0.46 +/- 0.011 mm compared with -0.016 +/- 0.006 mm) in 19SS men (P = 0.08). There was no effect of genotype on the response of these parameters to gemfibrozil treatment. These results shed new light on the role of APOA5 variants in TG metabolism and coronary heart disease risk.
动物和人体研究均支持载脂蛋白A-V（apoA-V）在甘油三酯（TG）代谢中发挥作用。我们在洛伐他汀冠状动脉造影试验中，研究了APOA5基因-1131T>C和S19W与血脂亚组分及动脉粥样硬化进展之间的关系。与-1131TT基因型男性（n = 242）相比，-1131C等位基因携带者（n = 54）的总TG水平显著更高（P = 0.03），这表现为极低密度脂蛋白（VLDL）质量显著增加[更高的VLDL-TG、VLDL-胆固醇、VLDL-蛋白质和表面脂质（均P < 0.05）]。由于apoB水平不受基因型影响，这表明VLDL大小增加而非数量增加。与19SS基因型男性（n = 268）相比，19W携带者（n = 44）的中间密度脂蛋白（IDL）-TG、IDL-胆固醇水平更高（P = 0.04），IDL表面成分[游离胆固醇（P = 0.005）和磷脂（P = 0.017）]也更高，但蛋白质含量无差异，这表明IDL脂质富集增加导致IDL大小增加。通过测量节段平均直径变化来评估，19W携带者的动脉粥样硬化进展也有增加趋势，19SS男性中节段平均直径变化为-0.46±0.011 mm，而19W携带者为-0.016±0.006 mm（P = 0.08）。基因型对这些参数接受吉非贝齐治疗的反应没有影响。这些结果为APOA5基因变异在TG代谢和冠心病风险中的作用提供了新的见解。
