Lack of association of the common TaqIB polymorphism in the cholesteryl ester transfer protein gene with angiographically assessed coronary atherosclerosis

Abstract

The anti-atherogenic effect of cholesteryl ester transfer protein (CETP) genetic variants associated with lowered enzyme activity is controversial. Moreover, in a few studies, this effect has been evaluated in the presence of a certain risk factor constellation. We addressed this issue in a case-control study, where 415 subjects with angiographically documented coronary artery disease (CAD +), 397 subjects without CAD (in 215, CAD was excluded by coronarography (CAD-)), and 188 healthy population controls, were screened for the CETP TaqIB polymorphism. The prevalence of the low-activity TaqIB2 allele was 0.396 in CAD+, and 0.428 and 0.416 in CAD- and population controls, respectively (p = 0.40). Its presence was significantly associated with increased high-density lipoprotein cholesterol (HDL-C) in population controls (1.40 +/- 0.40 mmol/l in B1B1, 1.52 +/- 0.39 mmol/l in B1B2 and 1.58 + 0.46 mmol/l in B2B2; p < 0.03 for trend), but not in the other groups. The CETP TaqIB polymorphism accounted for < 1% of the HDL-C variance in the whole cohort (p = 0.048). After adjustment for other risk factors, the CETP TaqIB2 allele was found not to be associated with significant changes in CAD risk independently of an assumed either dominant (odds ratio (OR) 0.97; 95% confidence interval (CI) 0.66-1.44; p = 0.89) or recessive effect (OR 0.68; 95% CI 0.42-1.12; p = 0.13). The CETP TaqIB polymorphism did not show a significant interaction with other risk factors in influencing CAD risk. Our findings do not support the hypothesis that a genetic variant resulting in lowered CETP activity is associated with reduced risk of coronary atherosclerosis.

Cholesteryl Ester Transfer Protein TaqIB Variant, High-Density Lipoprotein Cholesterol Levels, Cardiovascular Risk, and Efficacy of Pravastatin Treatment

“…A total of 9 population-based studies qualified for inclusion: 4 prospective studies: the Framingham Offspring Study (FOS), 20 the Physicians' Health Study (PHS), 21 the Northwick Park Heart Study (NPHS), 22 and the Reykjavik study; 23 and 5 cross-sectional studies: the European Atherosclerosis Research Study (EARS), 24 Etude Cas-Témoins de l'Infarctus du Myocarde (ECTIM), 15,25,26 the Oulu Project Elucidating Risk of Atherosclerosis (OPERA), 11,27 a study performed by Arca et al, 28 and one performed by Corella et al 29 Databases with individual patient data were obtained from all studies except for the FOS and the study performed by Corella et al 20,29 ; thus these 2 studies were not included. We identified 3 randomized, double-blind, placebo-controlled trials of pravastatin treatment wherein a subanalysis had been performed on the role of the TaqIB polymorphism: the Regression Growth Evaluation Statin Study (REGRESS), 7 the Cholesterol And Recurrent Events trial (CARE), 9 and the West of Scotland Coronary Prevention Study (WOSCOPS).…”

Carriers of three polymorphisms of cholesteryl ester transfer protein gene are at increased risk to coronary heart disease in a Chinese population

“…One of the most frequently studied polymorphisms in CETP gene, TaqIB, was reported to be associated with CETP activity and HDL-C level with B2 allele being related to lower CETP activity and higher HDL-C level [11,12]. However, some other similar studies showed conflicting results [13][14][15], and, moreover, no data on screening of SNPs in CETP gene in Chinese have ever been reported.…”

Natural genetic variation as a tool in understanding the role of CETP in lipid levels and disease

“…Nine hundred-twenty-five Japanese women were found to have more angina pectoris when they had the B1B1 genotype (P ϭ 0.03), while the effect was not statistically significant in 583 men (113). Other studies that have attempted to associate this polymorphism with CHD have also been limited by the size of the population needed to address this issue, even in an at-risk population (49,114,115).…”