Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk.
BACKGROUND
The importance of the cholesteryl ester transfer protein (CETP) pathway in coronary disease is uncertain. Study of CETP genotypes can help better understand the relevance of this pathway to lipid metabolism and disease risk.


OBJECTIVE
To assess associations of CETP genotypes with CETP phenotypes, lipid levels, and coronary risk.


METHODS
Studies published between January 1970 and January 2008 were identified through computer-based and manual searches using MEDLINE, EMBASE, BIOSIS, Science Citation Index, and the Chinese National Knowledge Infrastructure Database. Previously unreported studies were sought through correspondence with investigators.


METHODS
Relevant studies related principally to 3 common (TaqIB [rs708272], I405V [rs5882], and -629C>A [rs1800775]) and 3 uncommon (D442G [rs2303790], -631C>A [rs1800776], and R451Q [rs1800777]) CETP polymorphisms.


METHODS
Information on CETP genotypes, CETP phenotypes, lipid levels, coronary disease, and study characteristics was abstracted from publications, supplied by investigators, or both.


RESULTS
Ninety-two studies had data on CETP phenotypes, lipid levels, or both in 113,833 healthy participants, and 46 studies had data on 27,196 coronary cases and 55,338 controls. For each A allele inherited, individuals with the TaqIB polymorphism had lower mean CETP mass (-9.7%; 95% confidence interval [CI], -11.7% to -7.8%), lower mean CETP activity (-8.6%; 95% CI, -13.0% to -4.1%), higher mean high-density lipoprotein cholesterol (HDL-C) concentrations (4.5%; 95% CI, 3.8%-5.2%), and higher mean apolipoprotein A-I concentrations (2.4%; 95% CI, 1.6%-3.2%). The pattern of findings was very similar with the I405V and -629C>A polymorphisms. The combined per-allele odds ratios (ORs) for coronary disease were 0.95 (95% CI, 0.92-0.99) for TaqIB, 0.94 (95% CI, 0.89-1.00) for I405V, and 0.95 (95% CI, 0.91-1.00) for -629C>A.


CONCLUSIONS
Three CETP genotypes that are associated with moderate inhibition of CETP activity (and, therefore, modestly higher HDL-C levels) show weakly inverse associations with coronary risk. The ORs for coronary disease were compatible with the expected reductions in risk for equivalent increases in HDL-C concentration in available prospective studies.
Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge, England CB1 8RN.
Alexander
A
Thompson
Emanuele
E
Di Angelantonio
Nadeem
N
Sarwar
Sebhat
S
Erqou
Danish
D
Saleheen
Robin P F
RP
Dullaart
Bernard
B
Keavney
Zheng
Z
Ye
John
J
Danesh
D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics* / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood*; D010641:Phenotype; D012307:Risk Factors
D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008055:Lipids