Mitchell R J, Earl L, Bray P, Fripp Y J, Williams J
Department of Genetics and Human Variation, La Trobe University, Melbourne, Victoria, Australia.
Hum Biol. 1994 Jun;66(3):383-97.
Lipoprotein lipase (LPL) plays a critical role in the metabolism of lipoproteins because this enzyme hydrolyzes the triacylglycerides in chylomicrons and very low density lipoproteins. This process influences the production of high-density lipoprotein (HDL), which takes up tissue cholesterol for transport to the liver for excretion. Accordingly, LPL qualifies as a candidate gene for understanding lipid metabolic disorders and atherosclerosis. Studies on the relationship between genetic variation at the LPL locus and lipid phenotypes have produced equivocal results to date. To help clarify this issue, we investigated 144 outwardly healthy male Mediterranean migrants (from Italy and Greece), age between 40 and 70 years and resident in Australia, for associations between two common LPL restriction site polymorphisms and the following lipid and lipoprotein phenotypes: total plasma cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triacylglycerides. A series of analysis of variance tests, controlling for age, body mass index, and ethnicity, showed that the HindIII polymorphism at the LPL locus is significantly associated with both triacylglyceride and HDL cholesterol concentrations in this sample. The PvUII polymorphism, however, showed no association with any lipid. Kruskal-Wallis tests confirmed the significance of the associations between the HindIII RFLP and both HDL (p = 0.008) and triacylglycerides (p = 0.03). When the sample was subdivided into subjects who exhibited primary hypertriacylglyceridemia and normolipidemics, a significant difference was observed in the frequency of HindIII (p < 0.05) but not PvuII genotypes. HindIII heterozygotes (H1,H2) were least and H2,H2 individuals were most at risk for triacylglyceridemia. Examination of the normolipidemic sample revealed some evidence for an independent effect of the PvuII polymorphism on both LDL cholesterol and total cholesterol levels.
脂蛋白脂肪酶（LPL）在脂蛋白代谢中起关键作用，因为该酶可水解乳糜微粒和极低密度脂蛋白中的甘油三酯。这一过程会影响高密度脂蛋白（HDL）的产生，HDL可摄取组织中的胆固醇并转运至肝脏进行排泄。因此，LPL有资格作为理解脂质代谢紊乱和动脉粥样硬化的候选基因。迄今为止，关于LPL基因座的遗传变异与脂质表型之间关系的研究结果并不明确。为了帮助阐明这一问题，我们调查了144名外表健康的地中海男性移民（来自意大利和希腊），年龄在40至70岁之间，居住在澳大利亚，研究两种常见的LPL限制性位点多态性与以下脂质和脂蛋白表型之间的关联：总血浆胆固醇、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）和甘油三酯。一系列控制年龄、体重指数和种族的方差分析表明，该样本中LPL基因座的HindIII多态性与甘油三酯和HDL胆固醇浓度均显著相关。然而，PvUII多态性与任何脂质均无关联。Kruskal-Wallis检验证实了HindIII限制性片段长度多态性（RFLP）与HDL（p = 0.008）和甘油三酯（p = 0.03）之间关联的显著性。当将样本分为原发性高甘油三酯血症患者和血脂正常者时，观察到HindIII基因型频率存在显著差异（p < 0.05），而PvuII基因型频率无显著差异。HindIII杂合子（H1，H2）患甘油三酯血症的风险最低，而H2，H2个体风险最高。对血脂正常样本的检查发现，有证据表明PvuII多态性对LDL胆固醇和总胆固醇水平有独立影响。
