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Originally published In Press as doi:10.1194/jlr.M300420-JLR200 on March 16, 2004

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Journal of Lipid Research, Vol. 45, 1077-1083, June 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Relationship between cholesteryl ester transfer protein and LDL heterogeneity in familial hypercholesterolemia

Jean-Charles Hogue*, Benoît Lamarche*,{dagger}, Daniel Gaudet§, Mathieu Larivière*, André J. Tremblay*, Jean Bergeron*, Isabelle Lemieux**, Jean-Pierre Després**, Claude Gagné* and Patrick Couture1,*

* Lipid Research Center, CHUL Research Center and Laval University, Québec, Canada
{dagger} Institute on Nutraceuticals and Functional Foods, Laval University, Québec, Canada
§ Lipid Clinic, Centre Hospitalier de la Sagamie, Saguenay, Canada
** Quebec Heart Institute, Laval Hospital Research Center, Laval University, Québec

1 To whom correspondence should be addressed. e-mail: patrick.couture{at}crchul.ulaval.ca

Small, dense LDL particles have been associated with an increased risk of coronary artery disease, and cholesteryl ester transfer protein (CETP) has been suggested to play a role in LDL particle remodeling. We examined the relationship between LDL heterogeneity and plasma CETP mass in familial hypercholesterolemia (FH). LDL particles were characterized by polyacrylamide gradient gel electrophoresis in a total of 259 FH heterozygotes and 208 nonFH controls. CETP mass was measured by enzyme-linked immunosorbent assay in a subgroup of 240 participants, which included 120 FH patients matched with 120 controls. As compared with controls, FH subjects had an 11% higher CETP mass. Moreover, LDL-peak particle diameter (LDL-PPD) was significantly smaller in FH heterozygotes than in controls (258.1 ± 4.8 vs. 259.2 ± 4.1 Å; P = 0.01) after adjustment for covariates. There was also an inverse relationship between LDL-PPD and CETP mass (R = –0.15; P = 0.02), and this relationship was abolished by adjustment for the FH/control status, indicating that LDL-PPD changes in FH are mediated, at least in part, by an increase in plasma CETP mass concentrations.

These results suggest that increased plasma CETP mass concentrations could lead to significant LDL particle remodeling in FH heterozygotes and could contribute to the pathogenesis of atherosclerosis.

Abbreviations: apoE3, apolipoprotein E3; BMI, body mass index; CAD, coronary artery disease; CETP, cholesteryl ester transfer protein; FH, familial hypercholesterolemia; LDL-C, LDL cholesterol; LDL-PPD, LDL-peak particle diameter; LDLR, LDL receptor

Supplementary key words atherosclerosis • enzyme-linked immunosorbent assay • low density lipoprotein size


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