Cholesteryl Ester Transfer Protein Taq1B Research Articles

The cholesteryl ester transfer protein Taq1B gene polymorphism predicts clinical benefit of statin therapy in patients with significant coronary artery disease

Background Cholesteryl ester transfer protein (CETP) regulates plasma lipid distribution. A polymorphism in the CETP gene ( Taq1B) is associated with CETP activity, HDL concentration, atherosclerosis progression, and response to statins, and may influence cardiovascular (CV) events. We studied CETP Taq1B genotype, plasma HDL, and clinical events among all patients and patients stratified by statin treatment. Methods Consenting patients (n = 2531) with significant coronary artery disease (≥1 lesion of ≥70% stenosis) undergoing coronary arteriography were genotyped, grouped by statin prescription at hospital discharge, and prospectively followed-up for the outcomes of all-cause mortality and myocardial infarction. Results CETP Taq1B genotype frequencies were: B1B1, 32.9%; B1B2, 50.3%; and B2B2 16.8%. Plasma HDL was reduced for B1B1 patients (33 ± 12 mg/dL, vs 36 ± 13 mg/dL and 36 ± 13 mg/dL for B1B2 and B2B2, respectively, P for trend = .003). Overall, event rates did not differ between genotypes. Event rates were similar among untreated (24.8%) and statin-treated (24.2%) B1 homozygotes ( P = NS); statins significantly reduced events for B1B2 subjects (28.0% vs 21.0%, P = .009) and for B2B2 subjects (26.4% vs 17.4%, P = .048). Therapeutic benefit for B2 carriers remained after adjustment for covariates, and regression interaction analysis showed that B2 carriers experienced reduced events (relative risk [RR] 0.62, 95% CI 0.45–0.86), but statins did not benefit those with B1B1 (RR 1.09, 95% CI 0.70–1.7; P for interaction = .02). Findings were similar for the end point of death alone, although a modest benefit was seen in B1B1 patients (RR 0.67, P = .10), in addition to the strong benefit for B1B2 (RR 0.53, P = .001) and B2B2 (RR 0.28, P = .001). Conclusions The CETP Taq1B polymorphism is associated with differential HDL levels but no significant differential in CV risk in the absence of treatment. Importantly, however, CV event reduction by statin therapy is substantially enhanced in the presence of a B2 allele. Our findings suggest, for the first time, the potential of CETP Taq1B genotyping to enable more effective, pharmacogenetically directed therapy.

The association of cholesteryl ester transfer protein polymorphism with high-density lipoprotein cholesterol and coronary artery disease in Koreans.

Cholesteryl ester transfer protein (CETP) is a key protein involved in high-density lipoprotein cholesterol (HDL-C) metabolism. It is known to affect plasma HDL-C levels, and its genetic regulation may be involved in the development of coronary artery disease (CAD). The aim of this study was to determine the frequency of the CETP Taq1B polymorphism in Koreans, and to investigate its relationship with plasma HDL-C levels and CAD. One-hundred and nineteen patients with significant CAD and 106 controls were examined with respect to their genotypes, lipid profiles and other risk factors of CAD. The genotype frequencies of B1B1:B1B2:B2B2 in males and females were 35.5%:50%:14.5% and 34.7%:42.6%:22.7%, respectively, which is comparable to previous reports in other ethnic groups. The B1B1 homozygote was associated with significantly lower HDL-C levels in females (p = 0.049) and non-smoking males (p = 0.037). After controlling for gender, body mass index (BMI) and smoking, the TaqIB polymorphism was still significantly associated with HDL-C levels (p = 0.046) and explained 5.4% of the HDL-C variation in this study. By univariate analysis, the B1B1 homozygote was a significant predictor of CAD (p = 0.043), and this was confirmed by multivariate analysis with traditional risk factors, i.e. the B1B1 homozygote was an independent predictor of CAD (p = 0.026, odds ratio = 1.97, 95% confidence interval: 1.08-3.57). In conclusion, the B1B1 homozygote of the CETP Taq1B polymorphism is associated with low HDL-C levels in females and non-smoking males, and may be an independent genetic risk factor of CAD in the Korean population.

The B1B1 genotype of the cholesteryl ester transfer protein TAQ1B polymorphism is a novel risk factor in the development of coronary artery disease in Koreans

It has been suggested that apolipoprotein E (apoE) is inherited at a single genetic locus with three common alleles designated E2, E3, and E4. The products of these three alleles are apoE2, apoE3, and apoE4. The apoE phenotypes of 74 normal subjects and 226 hyperlipoproteinaemic subjects were ascertained by gel isoelectrofocusing. Patients with type I, type IIa, type IIb, and type IV hyperlipoproteinaemia had an apoE phenotypic distribution which was similar to that of normal subjects, with 40·0 to 60·0% being homozygous for E3. In contrast, 75% of type III patients had an E2 phenotype and 25% were E2/3heterozygotes. Among type V patients 31·4% had an E4 phenotype, and 42·9% were E4 heterozygotes. No type III patient and only 5·7% of type V patients had E3 phenotype. The results suggest that apoE2 and apoE4 are associated with two distinctly different dyslipoproteinaemias and that apoE has at least two different physiological functions.