© 1999 American Heart Association, Inc.
Original Contributions |
The T Allele of the Hepatic Lipase Promoter Variant C-480T Is Associated With Increased Fasting Lipids and HDL and Increased Preprandial and Postprandial LpCIII:B
European Atherosclerosis Research Study (EARS) II
From the Department of Internal Medicine III and Biochemistry, Erasmus University, Rotterdam, The Netherlands (H.J.); the Department of Medicine, Rayne Institute, University College Medical School, London, UK (G.C., P.J.T.); the Department of Biochemistry, National Public Health Institute, Helsinki, Finland (C.E.); Unité INSERM-325, Pasteur Institute, Lille, France (J.D.); and INSERM U258, Hôpital Broussais, Paris, France (V.N.).
Correspondence to Hans Jansen, PhD, Department of Biochemistry, Ee 671, Erasmus University Rotterdam, POB 1738, 3000 DR Rotterdam, Netherlands. E-mail jansen{at}bc1.fgg.eur.nl
Abstract—The common C-480T transition in the hepatic lipase (HL) promoter has been shown to be associated with lower HL activity and increased high density lipoprotein (HDL) cholesterol. We examined the frequency and lipid associations of this HL polymorphism in 385 healthy, young (18- to 28-year-old) men whose fathers had had a premature myocardial infarction (designated cases) and 405 age-matched controls. These individuals were participants in the European Atherosclerosis Research Study II postprandial trial, who had been recruited from 11 European countries in 4 regions (the Baltic; United Kingdom; and central and southern Europe). Overall, the frequency of the T allele was 0.207 in controls and 0.244 in cases (P=0.08). The T allele was associated with higher fasting plasma total cholesterol (P<0.01), triglycerides (P<0.01), and HDL cholesterol (P<0.01). The strongest association was found with apolipoprotein (apo) A-I concentration, which was 10% higher in individuals homozygous for the T allele compared with those homozygous for the C allele (P<0.001). This polymorphism had no effect on the rise in plasma triglyceride levels after a fatty meal. However, before and after the fat load was ingested, levels of particles containing both apoC-III and apoB (LpC-III:B) were higher in carriers of the T allele, with homozygotes having 23% and 27% higher levels preprandially and postprandially, respectively, than those homozygous for the C allele (P<0.05). Thus, our results demonstrate that the C-480T polymorphism in the HL promoter is associated with alterations in plasma lipids and lipoproteins and the accumulation of atherogenic LpC-III:B particles.
Key Words: hepatic lipase • gene promoter • polymorphisms • postprandial • lipoproteins
This article has been cited by other articles:
 |
|
 |
|
  P. Borel, M. Moussa, E. Reboul, B. Lyan, C. Defoort, S. Vincent-Baudry, M. Maillot, M. Gastaldi, M. Darmon, H. Portugal, et al. Human Plasma Levels of Vitamin E and Carotenoids Are Associated with Genetic Polymorphisms in Genes Involved in Lipid Metabolism J. Nutr., December 1, 2007; 137(12): 2653 - 2659. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Baum, M. C.Y. Ng, W.-Y. So, V. K.L. Lam, Y. Wang, E. Poon, B. Tomlinson, S. Cheng, K. Lindpaintner, and J. C.N. Chan Effect of Hepatic Lipase -514C->T Polymorphism and Its Interactions With Apolipoprotein C3 -482C->T and Apolipoprotein E Exon 4 Polymorphisms on the Risk of Nephropathy in Chinese Type 2 Diabetic Patients Diabetes Care, July 1, 2005; 28(7): 1704 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zhang, R. Lopez-Ridaura, E. B Rimm, N. Rifai, D. J Hunter, and F. B Hu Interactions between the -514C->T polymorphism of the hepatic lipase gene and lifestyle factors in relation to HDL concentrations among US diabetic men Am. J. Clinical Nutrition, June 1, 2005; 81(6): 1429 - 1435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Santamarina-Fojo, H. Gonzalez-Navarro, L. Freeman, E. Wagner, and Z. Nong Hepatic Lipase, Lipoprotein Metabolism, and Atherogenesis Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1750 - 1754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Isaacs, F. A. Sayed-Tabatabaei, O. T. Njajou, J. C. M. Witteman, and C. M. van Duijn The -514 C->T Hepatic Lipase Promoter Region Polymorphism and Plasma Lipids: A Meta-Analysis J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3858 - 3863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Hokanson, M. I. Kamboh, S. Scarboro, R. H. Eckel, and R. F. Hamman Effects of the Hepatic Lipase Gene and Physical Activity on Coronary Heart Disease Risk Am. J. Epidemiol., November 1, 2003; 158(9): 836 - 843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E S. Tai, D. Corella, M. Deurenberg-Yap, J. Cutter, S. K. Chew, C. E. Tan, and J. M. Ordovas Dietary Fat Interacts with the -514C>T Polymorphism in the Hepatic Lipase Gene Promoter on Plasma Lipid Profiles in a Multiethnic Asian Population: The 1998 Singapore National Health Survey J. Nutr., November 1, 2003; 133(11): 3399 - 3408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wang, I. Le Roy, E. Nicodeme, R. Li, R. Wagner, C. Petros, G. A. Churchill, S. Harris, A. Darvasi, J. Kirilovsky, et al. Using Advanced Intercross Lines for High-Resolution Mapping of HDL Cholesterol Quantitative Trait Loci Genome Res., July 1, 2003; 13(7): 1654 - 1664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. V. Andersen, H. H. Wittrup, A. Tybjaerg-Hansen, R. Steffensen, P. Schnohr, and B.o. G. Nordestgaard Hepatic lipase mutations,elevated high-density lipoprotein cholesterol, and increased risk of ischemic heart disease: The Copenhagen City Heart Study J. Am. Coll. Cardiol., June 4, 2003; 41(11): 1972 - 1982. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Anderson and J. F. Carlquist Genetic polymorphisms of hepatic lipase and cholesteryl ester transfer protein, intermediate phenotypes, and coronary risk: Do they add up yet? J. Am. Coll. Cardiol., June 4, 2003; 41(11): 1990 - 1993. [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Su, S. Zhang, D. W. Nebert, L. Zhang, D. Huang, Y. Hou, L. Liao, and C. Xiao A novel allele in the promoter of the hepatic lipase is associated with increased concentration of HDL-C and decreased promoter activity J. Lipid Res., October 1, 2002; 43(10): 1595 - 1601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jansen, A. J. M. Verhoeven, and E. J. G. Sijbrands Hepatic lipase: a pro- or anti-atherogenic protein? J. Lipid Res., September 1, 2002; 43(9): 1352 - 1362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.C. Carr, A.F. Ayyobi, S.J. Murdoch, S.S. Deeb, and J.D. Brunzell Contribution of Hepatic Lipase, Lipoprotein Lipase, and Cholesteryl Ester Transfer Protein to LDL and HDL Heterogeneity in Healthy Women Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 667 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Lundahl, A. Hamsten, and F. Karpe Postprandial Plasma ApoB-48 Levels Are Influenced by a Polymorphism in the Promoter of the Microsomal Triglyceride Transfer Protein Gene Arterioscler. Thromb. Vasc. Biol., February 1, 2002; 22(2): 289 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Talmud, L. Berglund, E. M. Hawe, D. M. Waterworth, C. R. Isasi, R. E. Deckelbaum, T. Starc, H. N. Ginsberg, S. E. Humphries, and S. Shea Age-Related Effects of Genetic Variation on Lipid Levels: The Columbia University BioMarkers Study Pediatrics, September 1, 2001; 108(3): e50 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-H. H. Juo, Z. Han, J. D. Smith, L. Colangelo, and K. Liu romoter polymorphisms of hepatic lipase gene influence HDL2 but not HDL3 in African American men: CARDIA study J. Lipid Res., February 1, 2001; 42(2): 258 - 264. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Friedlander, P. J. Talmud, K. L. Edwards, S. E. Humphries, and M. A. Austin Sib-pair linkage analysis of longitudinal changes in lipoprotein risk factors and lipase genes in women twins J. Lipid Res., August 1, 2000; 41(8): 1302 - 1309. [Abstract] [Full Text]
|
|
|
|
|
|
D. M. Waterworth, J. A. Hubacek, J. Pitha, J. Kovar, R. Poledne, S. E. Humphries, and P. J. Talmud Plasma levels of remnant particles are determined in part by variation in the APOC3 gene insulin response element and the APOCI;-APOE cluster J. Lipid Res., July 1, 2000; 41(7): 1103 - 1109. [Abstract] [Full Text]
|
|
|
|
|
|
J. Pihlajamaki, L. Karjalainen, P. Karhapaa, I. Vauhkonen, M.-R. Taskinen, S. S. Deeb, and M. Laakso G-250A Substitution in Promoter of Hepatic Lipase Gene Is Associated With Dyslipidemia and Insulin Resistance in Healthy Control Subjects and in Members of Families With Familial Combined Hyperlipidemia Arterioscler. Thromb. Vasc. Biol., July 1, 2000; 20(7): 1789 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Allayee, K. M. Dominguez, B. E. Aouizerat, R. M. Krauss, J. I. Rotter, J. Lu, R. M. Cantor, T. W. A. de Bruin, and A. J. Lusis Contribution of the hepatic lipase gene to the atherogenic lipoprotein phenotype in familial combined hyperlipidemia J. Lipid Res., February 1, 2000; 41(2): 245 - 252. [Abstract] [Full Text]
|
|
|
|
|
|
M.C. Carr, A.F. Ayyobi, S.J. Murdoch, S.S. Deeb, and J.D. Brunzell Contribution of Hepatic Lipase, Lipoprotein Lipase, and Cholesteryl Ester Transfer Protein to LDL and HDL Heterogeneity in Healthy Women Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 667 - 673. [Abstract] [Full Text] [PDF]
|
|