Kakko S, Tamminen M, Päivänsalo M, Kauma H, Rantala A O, Lilja M, Reunanen A, Kesäniemi Y A, Savolainen M J
University of Oulu, Oulu, Finland, National Public Health Institute, Helsinki, Finland.
Eur J Clin Invest. 2001 Jul;31(7):593-602. doi: 10.1046/j.1365-2362.2001.00859.x.
Cholesteryl ester transfer protein (CETP) plays a major role in lipoprotein metabolism. We have screened the CETP gene for mutations and polymorphisms regulating high density lipoproteins cholesterol (HDL-C) levels and the development of atherosclerosis, and found some polymorphisms (I405V and R451Q) to have minor effects.
The purpose of this study was to investigate the combined effect of the several polymorphisms of the CETP gene so far found on HDL-C levels and carotid intima-media thickness (IMT), and, in addition, to study whether the recently found functional polymorphism in the promoter region of the CETP gene (C to A, - 629 relative to the first transcribed nucleotide) explains the previous associations due to linkage disequilibrium. The genotypes were determined in a population sample of 481 men and women.
There were no significant differences in plasma CETP activity or carotid IMT between the genotypes of the promoter polymorphism. The women with the CC genotype of the promoter polymorphism had the lowest HDL-C levels (P < 0.001), but no such difference was seen in men. Detected polymorphisms of the CETP gene explained about 8% of the variation in HDL-C in women and about 7 and 10% of the variation in carotid IMT in women and men, respectively. The associations of the promoter, I405V and R451Q-A373P polymorphisms with HDL-C and carotid IMT seemed to be independent of each other. The associations with IMT were independent of total HDL-C levels, suggesting that HDL subfractions may have more effect on IMT.
The CETP gene locus was found to be polymorphic and its polymorphisms explained a reasonable proportion of the variation in the degree of carotid atherosclerosis.
胆固醇酯转运蛋白（CETP）在脂蛋白代谢中起主要作用。我们已筛查CETP基因中调节高密度脂蛋白胆固醇（HDL-C）水平及动脉粥样硬化发展的突变和多态性，发现一些多态性（I405V和R451Q）影响较小。
本研究目的是调查迄今发现的CETP基因多种多态性对HDL-C水平和颈动脉内膜中层厚度（IMT）的联合作用，此外，研究CETP基因启动子区域最近发现的功能性多态性（C到A，相对于第一个转录核苷酸为 - 629）是否因连锁不平衡解释了先前的关联。在481名男性和女性的人群样本中确定基因型。
启动子多态性的不同基因型之间血浆CETP活性或颈动脉IMT无显著差异。启动子多态性CC基因型的女性HDL-C水平最低（P < 0.001），但男性未观察到这种差异。检测到的CETP基因多态性分别解释了女性HDL-C变异的约8%以及女性和男性颈动脉IMT变异的约7%和10%。启动子、I405V和R451Q - A373P多态性与HDL-C和颈动脉IMT的关联似乎相互独立。与IMT的关联独立于总HDL-C水平，表明HDL亚组分可能对IMT有更大影响。
发现CETP基因位点具有多态性，其多态性解释了颈动脉粥样硬化程度变异的合理比例。
