Association of the C-514T polymorphism in the hepatic lipase gene with variations in lipoprotein subclass profiles - The Framingham Offspring Study
Association of the C-514T polymorphism in the hepatic lipase gene with variations in lipoprotein subclass profiles - The Framingham Offspring Study
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DOI：
10.1161/01.atv.20.3.815
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发表时间：
2000-03-01
影响因子：
8.7
通讯作者：
Ordovas, JM
中科院分区：
文献类型：
--
作者：
Couture, P;Otvos, JD;Ordovas, JM
肝脂肪酶参与多种脂蛋白的代谢，并在胆固醇反向转运中发挥关键作用。肝脂肪酶启动子-514位的常见C-至-T取代与血浆高密度脂蛋白胆固醇（HDL-C）水平和肝脂肪酶活性的变化相关。本研究的目的是调查该多态性与1314名男性和1353名女性Frachial Offspring研究参与者中脂蛋白水平的相关性。在男性和女性中，-514T等位基因携带者与非携带者相比，HDL-C和载脂蛋白A-I（apoAI）浓度更高。与-514T等位基因相关的高密度脂蛋白胆固醇水平升高是由于高密度脂蛋白2-胆固醇亚组分的增加，与男性相比，女性中这种相关性更强（P=0.0043 vs 0.0517）。为了进一步了解这些作用的代谢基础，分别使用自动核磁共振光谱和梯度凝胶电泳测量HDL和低密度脂蛋白（LDL）亚类谱。在男性和女性中观察到的-514T等位基因与较高HDL-C水平的相关性主要是由于大HDL亚组分（尺寸范围8.8至13.0 nm）的显著增加。相比之下，在校正了家庭关系、年龄、体重指数、吸烟、饮酒、β受体阻滞剂使用、apoE基因型、绝经状态和女性雌激素治疗后，-514位肝脂酶多态性与LDL粒径分布之间没有关系。多元回归分析显示，C-514 T多态性对男性和女性HDL颗粒大小的变异性有显著影响（P
Hepatic lipase is involved in the metabolism of several lipoproteins and has a key role in reverse cholesterol transport. A common C-to-T substitution at position -514 of the hepatic lipase promoter has been associated with variations in plasma high density lipoprotein cholesterol (HDL-C) levels and hepatic lipase activity. The aim of the current study was to investigate the association of this polymorphism to lipoprotein levels in a population-based sample of 1314 male and 1353 female Framingham Offspring Study participants. In men and women, carriers of the -514T allele had higher HDL-C and apolipoprotein A-I (apoAI) concentrations compared with noncarriers. The higher HDL-C levels associated with the -514T allele was due to an increase in the HDL2-C subfraction, and this association was stronger in women compared with men (P=0.0043 versus 0.0517). To gain further understanding about the metabolic basis of these effects, HDL and low density lipoprotein (LDL) subclass profiles were measured by using automated nuclear magnetic resonance spectroscopy and gradient gel electrophoresis, respectively. The association of the -514T allele with higher HDL-C levels seen in men and women was primarily due to significant increases in the large HDL subfractions (size range 8.8 to 13.0 nm). In contrast, there was no relationship between the hepatic lipase polymorphism at position -514 and the LDL particle size distribution after adjustment for familial relationships, age, body mass index, smoking, alcohol intake, use of beta-blockers, apoE genotype, and menopausal status and estrogen therapy in women. Moreover, multiple regression analyses suggested that the C-514T polymorphism contributed significantly to the variability of HDL particle size in men and women (P