四个载脂蛋白 E 基因多态性与冠心病的相关性研究。

Four polymorphisms of cholesteryl ester transfer protein gene and coronary stenosis in a Tunisian population.

机构信息

Biochemistry Department, Sahloul University Hospital, Sousse, Tunisia.

出版信息

J Cardiovasc Med (Hagerstown). 2012 Sep;13(9):546-53. doi: 10.2459/JCM.0b013e3283569b24.

DOI:10.2459/JCM.0b013e3283569b24

PMID:22854712

Abstract

AIMS

The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is under debate. We studied the association of four polymorphisms (Taq1B, I405V, R451Q and A373P) in the CETP gene with lipid profile and coronary artery disease.

METHODS

Four CETP polymorphisms were studied in 316 Tunisian patients undergoing coronary angiography. Patients were clinically examined and their lipid profiles were estimated. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism analysis.

RESULTS

The 451Q allele, associated with lower high-density lipoprotein-cholesterol (HDL-C) and higher total cholesterol and apolipoprotein B (ApoB) concentrations, was also significantly associated with an increased risk of significant stenosis [odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.15-2.61, P = 0.007]. The B2 allele of Taq1B polymorphism had an increase in HDL-C concentration and was associated with a decreased risk of coronary stenosis, as described earlier. It was also associated with low risk of hypoHDLaemia [OR = 0.615, 95% CI 0.377-1.002, P = 0.035]. No significant effect of different A373P and I405V alleles was found on the lipid profile and on coronary stenosis. When CETP polymorphisms were combined in haplotypes possessing R451Q, A373P, I405V, Taq1B polymorphisms, the 1112 haplotype (where 1 is the wild genotype and 2 represents carriers of the variant allele) seems to be the most protective against significant stenosis (OR = 0.71, 95% CI 0.188-0.983; P = 0.014), whereas 2111 was probably the most atherogenic, with an OR = 2.17, 95% CI 1.06-5.88; P = 0.039.

CONCLUSION

The Q allele of the R451Q polymorphism was associated with decreased HDL-C, increased ApoB concentrations and increased risk of coronary stenosis. In haplotype analysis, we found that 1112 seems to be a protective haplotype, whereas 2111 has an atherogenic effect in a coronary Tunisian population.

摘要

目的

胆固醇酯转移蛋白（CETP）在动脉粥样硬化发展中的作用仍存在争议。本研究旨在探讨 CETP 基因中的 4 种多态性（Taq1B、I405V、R451Q 和 A373P）与血脂谱和冠状动脉疾病的关系。

方法

对 316 例接受冠状动脉造影的突尼斯患者进行了 4 种 CETP 多态性研究。对患者进行临床检查，并估计其血脂谱。采用聚合酶链反应-限制性片段长度多态性分析进行基因分型。

结果

与高密度脂蛋白胆固醇（HDL-C）降低和总胆固醇及载脂蛋白 B（ApoB）浓度升高相关的 451Q 等位基因，与显著狭窄的风险增加显著相关[比值比（OR）=1.74，95%置信区间（CI）为 1.15-2.61，P=0.007]。Taq1B 多态性的 B2 等位基因可增加 HDL-C 浓度，与冠状动脉狭窄风险降低有关。它还与低危低 HDL-aemia 相关[OR=0.615，95%CI 0.377-1.002，P=0.035]。不同 A373P 和 I405V 等位基因对血脂谱和冠状动脉狭窄无显著影响。当 CETP 多态性组合为携带 R451Q、A373P、I405V、Taq1B 多态性的 1112 单倍型时，1112 单倍型似乎最能抵抗显著狭窄（OR=0.71，95%CI 0.188-0.983；P=0.014），而 2111 单倍型可能最具动脉粥样硬化性，OR=2.17，95%CI 1.06-5.88；P=0.039。