Genetic determinants of plasma triglycerides: impact of rare and common mutations.

被引:20
作者
Talmud P.J. [1 ]
机构
[1] Division of Cardiovascular Genetics, Department of Medicine, British Heart Foundation Laboratories, Royal Free and University College Medical School, 5 University Street
关键词
Lipoprotein Lipase; Arterioscler Thromb Vasc Biol; Lipoprotein Lipase Gene; Apolipoprotein CIII; APOC3 Gene;
D O I
10.1007/s11883-001-0061-4
中图分类号
学科分类号
摘要
Raised plasma triglyceride (TG) levels are an independent risk factor for coronary artery disease (CAD), and thus understanding the genetic and environmental determinants of TG levels are of major importance. TG metabolism is a process for delivering free fatty acids for energy storage or b-oxidation, and involves a number of different hydrolytic enzymes and apolipoproteins (apo). The genes encoding these proteins are, therefore, candidates for determining plasma TGs. Although rare mutations in lipoprotein lipase (LPL), the major TG-hydrolyzing enzyme, and apo CII (APOC2), its essential activator, result in extremely high plasma TG levels, their low frequency means they have little impact upon TG levels in the general population. Common mutations in LPL, apo CIII (APOC3), and apo E (APOE) have the strongest effect on plasma TG levels at the population level. In addition, environmental factors such as diet, obesity, and smoking interact with genetic determinants of TG to produce a modulating high-risk environment.
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页码:191 / 199
页数:8
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共 141 条
[1]  
Wilson PW(1996)High density lipoprotein cholesterol and mortality Arteriosclerosis 276 544-548
[2]  
Abbott RD(1996)Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies J Cardiovasc Risk 3 213-219
[3]  
Castelli WP(1998)Atherogenic, dense low-density lipoproteins. Pathophysiology and new therapeutic approaches Eur Heart J 19 A24-30
[4]  
Hokanson JE(1995)Triglyceride lipases and atherosclerosis Curr Opin Lipidol 6 291-305
[5]  
Austin MA(1991)Lipoprotein lipase enhances the binding of chylomicrons to low density lipoprotein receptor-related protein Proc Natl Acad Sci U S A 88 8342-8346
[6]  
Chapman MJ(1999)Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein E J Lipid Res 40 1-16
[7]  
Guerin M(1980)Evidence for the role of hepatic endothelial lipase in the metabolism of plasma high density lipoprotein2 in man Atherosclerosis 36 589-593
[8]  
Bruckert E(1994)The multifunctional role of hormone-sensitive lipase in lipid metabolism Adv Enzyme Regul 34 355-370
[9]  
Olivecrona G(1999)Role of ApoCs in lipoprotein metabolism: functional differences between ApoC1, ApoC2, and ApoC3 Arterioscler Thromb Vasc Biol 19 472-484
[10]  
Olivecrona T(1985)Modulation of lipoprotein lipase activity by apolipoproteins. Effect of apolipoprotein C-III J Clin Invest 75 384-390