Arca M, Montali A, Ombres D, Battiloro E, Campagna F, Ricci G, Verna R
Istituto di Terapia Medica Sistematica, Università degli Studi di Roma La Sapienza, Italy.
Clin Genet. 2001 Nov;60(5):374-80. doi: 10.1034/j.1399-0004.2001.600510.x.
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.
与酶活性降低相关的胆固醇酯转运蛋白(CETP)基因变异的抗动脉粥样硬化作用存在争议。此外,在一些研究中,这种作用是在特定风险因素组合的情况下进行评估的。我们在一项病例对照研究中解决了这个问题,该研究对415例经血管造影证实患有冠状动脉疾病的受试者(CAD+)、397例无CAD的受试者(其中215例经冠状动脉造影排除CAD(CAD-))以及188例健康人群对照进行了CETP TaqIB多态性筛查。低活性TaqIB2等位基因在CAD+中的患病率为0.396,在CAD-和人群对照中分别为0.428和0.416(p = 0.40)。在人群对照中,其存在与高密度脂蛋白胆固醇(HDL-C)升高显著相关(B1B1为1.40±0.40 mmol/l,B1B2为1.52±0.39 mmol/l,B2B2为1.58 + 0.46 mmol/l;趋势p < 0.03),但在其他组中并非如此。CETP TaqIB多态性在整个队列中占HDL-C变异的比例<1%(p = 0.048)。在对其他风险因素进行调整后,发现CETP TaqIB2等位基因与CAD风险的显著变化无关,无论假设其为显性效应(优势比(OR)0.97;95%置信区间(CI)0.66 - 1.44;p = 0.89)还是隐性效应(OR 0.68;95% CI 0.42 - 1.12;p = 0.13)。CETP TaqIB多态性在影响CAD风险方面未显示出与其他风险因素的显著相互作用。我们的研究结果不支持以下假设:导致CETP活性降低的基因变异与冠状动脉粥样硬化风险降低相关。