TaqIB polymorphism in cholesterol ester transfer protein (CETP) gene predicts future cardiovascular death in patients experiencing an acute coronary syndrome.
BACKGROUND
Cholesterol ester transfer protein (CETP) plays a pivotal role in the remodelling of triglyceride (TG)-rich and high-density lipoprotein (HDL) particles. Sequence variations in the CETP gene may interfere with coronary atherosclerosis. However, clinical studies of various CETP polymorphisms have shown controversial data in coronary artery outcome. We aimed to investigate whether TaqIB CETP gene polymorphism could predict clinical outcome in a prospective cohort of patients hospitalized for an acute coronary syndrome (ACS).


METHODS
Two hundred and seventy consecutive Caucasian patients hospitalized for an ACS, and having a significant coronary artery disease in at least one major vessel (stenosis >50%), were prospectively enrolled and followed for 57 months. The mean age was 65.1+/-12.5 years, and 77% were males. One hundred and thirty-nine patients (51.5%) suffered from unstable angina at inclusion and 131 patients (48.5%) presented with an acute myocardial infarction (MI). The follow-up data were obtained from questionnaires. The major recurrent events recorded were 32 deaths comprising 28 cardiovascular deaths and 49 combined cardiovascular events (28 cardiovascular deaths, 19 non-fatal ACS and 2 non-fatal strokes). CETP genotyping was performed using a restriction fragment length polymorphism based method.


RESULTS
A significant relation was found between B2B2 genotype and combined cardiovascular end-point (p<0.02), mainly driven by a link with cardiovascular death (p<0.05). The hazard risk ratio for cardiovascular death associated with B2B2 genotype was 2.2 [95% confidence interval (CI): 1.01-4.94, p<0.05]. In multivariate analyses, no modification except for a significant interaction with statin therapy was observed by inclusion of potential confounders for the association of B2B2 genotype with cardiovascular death.


CONCLUSIONS
These results suggest that patients homozygous for the B2 allele and not taking statin had a strong increase of recurrent cardiovascular event after an initial acute coronary event. This cardiovascular risk seems to be corrected with statin therapy.
Pillois
Xavier
X
Institut Fédératif de Recherche, n(o) 4 "Heart-Lung-Vessel-Thrombosis", University Victor Segalen of Bordeaux, France.
Phuong Do Thi
Nahm
N
Reynaud
Annabel
A
Benchimol
Daniel
D
Lagrost
Laurent
L
Bonnet
Jacques
J
D054058:Acute Coronary Syndrome / Q000235:genetics / Q000401:mortality* / Q000628:therapy; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016019:Survival Analysis
D000924:Anticholesteremic Agents; D053480:Cholesterol Ester Transfer Proteins