Juo S H, Han Z, Smith J D, Colangelo L, Liu K
Columbia Genome Center, Columbia University, New York, NY 10032, USA.
J Lipid Res. 2001 Feb;42(2):258-64.
Hepatic lipase encoded by the hepatic lipase gene (LIPC) is involved in the metabolism of several lipoproteins. Four promoter polymorphisms in LIPC have been found to be in complete disequilibrium and associated with high density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo)A-I levels in both white and black populations. We investigated the association between the promoter polymorphism and lipid profiles as well as anthropometric phenotypes in African American men in the Coronary Artery Risk Development in Young Adults study. We performed serial cross-sectional analyses and longitudinal analyses of lipids from 578 subjects in five examinations over 10 years of follow-up. Results showed that the allele frequency (0.52) in our black population was consistent with that reported in black subjects but much higher than that reported (approximately 0.2) in white populations. Analysis of covariance tests of the three genotypic means in each examination showed that the P values ranged from 0.01 to 0.08 for HDL-C (except P = 0.54 in the fourth examination), from 0.006 to 0.01 for HDL(2)-C, and from 0.06 to 0.07 for apoA-I. Mean HDL(3)-C levels were essentially identical among the three genotypes. Total cholesterol, low density lipoprotein cholesterol (LDL-C), triglycerides, and apoB, which are mainly involved in the very low density lipoprotein-LDL pathway, were not significantly different according to the promoter polymorphism, except for triglycerides in the third examination (P = 0.01). No significant association was found between anthropometric phenotypes and the LIPC polymorphism in any of five examinations. The change of the anthropometric variables was not significantly associated with genotypes. In conclusion, our results indicated that the LIPC promoter polymorphism has exclusive effects on HDL(2)-C but not HDL(3)-C levels.
由肝脂肪酶基因(LIPC)编码的肝脂肪酶参与多种脂蛋白的代谢。已发现LIPC中的四种启动子多态性处于完全不平衡状态,并且在白人和黑人人群中均与高密度脂蛋白胆固醇(HDL-C)和载脂蛋白(apo)A-I水平相关。在“青年成人冠状动脉风险发展”研究中,我们调查了非洲裔美国男性中启动子多态性与血脂谱以及人体测量学表型之间的关联。我们对578名受试者在10年随访期间的五次检查中的血脂进行了系列横断面分析和纵向分析。结果显示,我们黑人人群中的等位基因频率(0.52)与黑人受试者中报告的频率一致,但远高于白人人群中报告的频率(约0.2)。每次检查中三种基因型均值的协方差分析表明,HDL-C的P值范围为0.01至0.08(第四次检查中P = 0.54除外),HDL(2)-C的P值范围为0.006至0.01,apoA-I的P值范围为0.06至0.07。三种基因型的平均HDL(3)-C水平基本相同。主要参与极低密度脂蛋白-LDL途径的总胆固醇、低密度脂蛋白胆固醇(LDL-C)、甘油三酯和apoB,除第三次检查中的甘油三酯外(P = 0.01),根据启动子多态性无显著差异。在五次检查中的任何一次中,均未发现人体测量学表型与LIPC多态性之间存在显著关联。人体测量学变量的变化与基因型无显著关联。总之,我们的结果表明,LIPC启动子多态性对HDL(2)-C水平有独特影响,但对HDL(3)-C水平无影响。