Authors |
Thompson
A, Di Angelantonio E, Sarwar N, Erqou S, Saleheen D, Dullaart RP, Keavney
B, Ye Z, Danesh J.
|
Abstract
|
CONTEXT
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.
DATA SOURCES 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.
STUDY SELECTION 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.
DATA EXTRACTION 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 highdensity 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.
|