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.
Biochim Biophys Acta
; 1781(1-2): 10-5, 2008.
Article
in En
| MEDLINE
| ID: mdl-18178167
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), lecithincholesterol 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Plasma
/
Polymorphism, Genetic
/
Cholesterol
/
Promoter Regions, Genetic
/
Cholesterol Ester Transfer Proteins
/
Fibroblasts
/
Phosphatidylcholine-Sterol O-Acyltransferase
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
/
Male
Language:
En
Journal:
Biochim Biophys Acta
Year:
2008
Document type:
Article
Affiliation country:
Países Bajos