This Article Full Text Full Text (PDF) All Versions of this Article: 22/4/667    most recent 01.ATV.0000013284.47317.95v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carr, M.C. Articles by Brunzell, J.D. Search for Related Content PubMed PubMed Citation Articles by Carr, M.C. Articles by Brunzell, J.D. Related Collections Pathophysiology Risk Factors Genetics of cardiovascular disease Lipid and lipoprotein metabolism

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:667.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Contribution of Hepatic Lipase, Lipoprotein Lipase, and Cholesteryl Ester Transfer Protein to LDL and HDL Heterogeneity in Healthy Women

M.C. Carr; A.F. Ayyobi; S.J. Murdoch; S.S. Deeb; J.D. Brunzell

From the Division of Metabolism, Endocrinology, and Nutrition (M.C.C., A.F.A., S.J.M., J.D.B.) and the Division of Medical Genetics (S.S.D.), University of Washington, Seattle.

Correspondence to John D. Brunzell, MD, Division of Metabolism, Endocrinology, and Nutrition, Box 356426, University of Washington, Seattle, WA 98195-6426. E-mail brunzell{at}u.washington.edu

Hepatic lipase (HL) and cholesteryl ester transfer protein (CETP) have been independently associated with low density lipoprotein (LDL) and high density lipoprotein (HDL) size in different cohorts. These studies have been conducted mainly in men and in subjects with dyslipidemia. Ours is a comprehensive study of the proposed biochemical determinants (lipoprotein lipase, HL, CETP, and triglycerides) and genetic determinants (HL gene [LIPC] and Taq1B) of small dense LDL (sdLDL) and HDL subspecies in a large cohort of 120 normolipidemic, nondiabetic, premenopausal women. HL (P<0.001) and lipoprotein lipase activities (P=0.006) were independently associated with LDL buoyancy, whereas CETP (P=0.76) and triglycerides (P=0.06) were not. The women with more sdLDL had higher HL activity (P=0.007), lower HDL2 cholesterol (P<0.001), and lower frequency of the HL (LIPC) T allele (P=0.034) than did the women with buoyant LDL. The LIPC variant was associated with HL activity (P<0.001), HDL2 cholesterol (P=0.034), and LDL buoyancy (P=0.03), whereas the Taq1B polymorphism in the CETP gene was associated with CETP mass (P=0.002) and HDL3 cholesterol (P=0.039). These results suggest that HL activity and HL gene promoter polymorphism play a significant role in determining LDL and HDL heterogeneity in healthy women without hypertriglyceridemia. Thus, HL is an important determinant of sdLDL and HDL2 cholesterol in normal physiological states as well as in the pathogenesis of various disease processes.

Key Words: cholesterol • triglycerides • Taq1B variant • LIPC • polymorphisms

This article has been cited by other articles:

				S. Fazio and M. F. Linton Elevated High-Density Lipoprotein (HDL) Levels due to Hepatic Lipase Mutations Do Not Reduce Cardiovascular Disease Risk: Another Strike against the HDL Dogma J. Clin. Endocrinol. Metab., April 1, 2009; 94(4): 1081 - 1083. [Full Text] [PDF]

				A. Thompson, E. Di Angelantonio, N. Sarwar, S. Erqou, D. Saleheen, R. P. F. Dullaart, B. Keavney, Z. Ye, and J. Danesh Association of Cholesteryl Ester Transfer Protein Genotypes With CETP Mass and Activity, Lipid Levels, and Coronary Risk JAMA, June 18, 2008; 299(23): 2777 - 2788. [Abstract] [Full Text] [PDF]

				B. Kaess, M. Fischer, A. Baessler, K. Stark, F. Huber, W. Kremer, H. R. Kalbitzer, H. Schunkert, G. Riegger, and C. Hengstenberg The lipoprotein subfraction profile: heritability and identification of quantitative trait loci J. Lipid Res., April 1, 2008; 49(4): 715 - 723. [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]

				D. R. Witte, M. R. Taskinen, H. Perttunen-Nio, A. van Tol, S. Livingstone, and H. M. Colhoun Study of agreement between LDL size as measured by nuclear magnetic resonance and gradient gel electrophoresis J. Lipid Res., June 1, 2004; 45(6): 1069 - 1076. [Abstract] [Full Text] [PDF]

				J.-C. Hogue, B. Lamarche, D. Gaudet, M. Lariviere, A. J. Tremblay, J. Bergeron, I. Lemieux, J.-P. Despres, C. Gagne, and P. Couture Relationship between cholesteryl ester transfer protein and LDL heterogeneity in familial hypercholesterolemia J. Lipid Res., June 1, 2004; 45(6): 1077 - 1083. [Abstract] [Full Text] [PDF]

				Y. Bosse, L. Perusse, and M.-C. Vohl Genetics of LDL particle heterogeneity: from genetic epidemiology to DNA-based variations J. Lipid Res., June 1, 2004; 45(6): 1008 - 1026. [Abstract] [Full Text] [PDF]

				G. Bos, P. G. Scheffer, D. Vieira, J. M. Dekker, G. Nijpels, M. Diamant, T. Teerlink, C. D.A. Stehouwer, L. M. Bouter, R. J. Heine, et al. The Relationship of Lipoprotein Lipase Activity and LDL size Is Dependent on Glucose Metabolism in an Elderly Population: The Hoorn Study Diabetes Care, March 1, 2004; 27(3): 796 - 798. [Full Text] [PDF]

				F. M. Sacks and H. Campos Low-Density Lipoprotein Size and Cardiovascular Disease: A Reappraisal J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4525 - 4532. [Full Text] [PDF]

				J.-F. Mauger, A. H Lichtenstein, L. M Ausman, S. M Jalbert, M. Jauhiainen, C. Ehnholm, and B. Lamarche Effect of different forms of dietary hydrogenated fats on LDL particle size Am. J. Clinical Nutrition, September 1, 2003; 78(3): 370 - 375. [Abstract] [Full Text] [PDF]

				M. Guerin, W. Le Goff, E. Frisdal, S. Schneider, D. Milosavljevic, E. Bruckert, and M. J. Chapman Action of Ciprofibrate in Type IIB Hyperlipoproteinemia: Modulation of the Atherogenic Lipoprotein Phenotype and Stimulation of High-Density Lipoprotein-Mediated Cellular Cholesterol Efflux J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3738 - 3746. [Abstract] [Full Text] [PDF]

				A. Soro, M. Jauhiainen, C. Ehnholm, and M.-R. Taskinen Determinants of low HDL levels in familial combined hyperlipidemia J. Lipid Res., August 1, 2003; 44(8): 1536 - 1544. [Abstract] [Full Text] [PDF]

				S. M. Boekholdt and J. F. Thompson Natural genetic variation as a tool in understanding the role of CETP in lipid levels and disease J. Lipid Res., July 1, 2003; 44(6): 1080 - 1093. [Abstract] [Full Text] [PDF]

				S. Y. Choi, K.-i. Hirata, T. Ishida, T. Quertermous, and A. D. Cooper Endothelial lipase: a new lipase on the block J. Lipid Res., November 1, 2002; 43(11): 1763 - 1769. [Abstract] [Full Text] [PDF]