The ability of plasma to stimulate fibroblast cholesterol efflux is associated with the -629C-->A cholesteryl ester transfer protein promoter polymorphism: role of lecithin: cholesterol acyltransferase activity

Biochimica Et Biophysica Acta
Susanna E BorggreveR P F Dullaart

Abstract

A recent population-based study showed that cholesteryl ester transfer protein (CETP) gene variations, which relate to lower plasma CETP, may predict increased cardiovascular risk, in spite of higher HDL cholesterol. Among other functions, CETP activity contributes to cellular cholesterol efflux, an early step in the anti-atherogenic reverse cholesterol transport (RCT) process. We hypothesized that cellular cholesterol efflux stimulating capacity of plasma could be associated with CETP gene variation. In this study, we tested the extent to which the ability of plasma to promote cholesterol efflux from cultured human fibroblasts is associated with CETP gene variation. In 223 men, the -629C-->A CETP promoter polymorphism, plasma lipids, CETP mass, cholesteryl ester transfer (CET), lecithin:cholesterol acyltransferase (LCAT) activity and the ability of plasma to promote cholesterol efflux from human skin fibroblasts, obtained from a single normolipidemic donor, were determined. In -629CC homozygotes (n=52), cholesterol efflux, plasma CETP mass, CET and LCAT activity were higher, whereas HDL cholesterol was lower compared to -629 AA homozygotes (n=62) and -629CA+AA carriers (n=171) (P<0.05 to P<0.001). Univariate correlation analys...Continue Reading

Citations

May 24, 2014·Nature Reviews. Drug Discovery·Bronwyn A KingwellNorman E Miller
Jul 16, 2008·Expert Opinion on Therapeutic Targets·Ekaterini Vourvouhaki, George V Dedoussis
May 20, 2008·Cardiovascular Therapeutics·Cesare R Sirtori, Giuliana Mombelli
Jul 22, 2010·Cardiovascular Therapeutics·Paul J W H KappelleRobin P F Dullaart
Feb 2, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Elise F VillardMaryse Guerin
Sep 5, 2014·F1000Research·Norman E Miller

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