Genetics
CETP promoter variant linked to lower CETP levels also impairs the ability of plasma to remove cholesterol from cells, a possible clue to its cardiovascular risk (Biochim Biophys Acta 2008)
Original title: 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
Since CETP gene variation linked to lower plasma CETP had recently been shown to predict increased cardiovascular risk despite higher HDL-cholesterol, this study tested whether the ability of plasma to promote cholesterol efflux from cultured human fibroblasts, an early step in reverse cholesterol transport, is associated with the -629C to A CETP promoter polymorphism, measured in 223 men alongside plasma lipids, CETP mass, cholesteryl ester transfer (CET), and LCAT activity. In -629CC homozygotes (n=52), cholesterol efflux, plasma CETP mass, CET, and LCAT activity were all higher, while HDL-cholesterol was lower, than in -629AA homozygotes (n=62) and CA plus AA carriers (n=171) combined (P less than 0.05 to P less than 0.001). Cellular cholesterol efflux correlated with CETP genotype (P=0.04), plasma CET (P less than 0.05), LCAT activity (P less than 0.001), and apoA-I (P less than 0.05), with multiple regression confirming an independent association between cholesterol efflux and CETP genotype.
Original 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 analysis showed that cellular cholesterol efflux was related to CETP genotype (P=0.04), plasma CET (P<0.05), LCAT activity (P<0.001) and apo A-I (P<0.05). Multiple linear regression analysis confirmed the independent association of cellular cholesterol efflux to plasma with CETP genotype. In conclusion, an association of cellular cholesterol efflux with the -629C-->A CETP polymorphism, possibly also involving LCAT activity, could provide a mechanism explaining why CETP gene variation, which relates to lower plasma CETP, does not confer diminished cardiovascular risk.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.