胆固醇酯转运蛋白编码基因TaqIB多态性与中年男性心肌梗死风险的前瞻性研究。

A prospective study of TaqIB polymorphism in the gene coding for cholesteryl ester transfer protein and risk of myocardial infarction in middle-aged men.

作者信息

Liu Simin, Schmitz Christian, Stampfer Meir J, Sacks Frank, Hennekens Charles H, Lindpaintner Klaus, Ridker Paul M

机构信息

Division of Preventive Medicine, Department of Medicine, Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School, 900 Commonwealth Avenue East, Boston, MA 02215, USA.

出版信息

Atherosclerosis. 2002 Apr;161(2):469-74. doi: 10.1016/s0021-9150(01)00673-6.

DOI:10.1016/s0021-9150(01)00673-6

PMID:11888533

Abstract

BACKGROUND

Molecular variations in the gene coding for the cholesteryl ester transfer protein (CETP) such as the TaqIB polymorphism are associated with higher plasma high-density lipoprotein (HDL) concentration. However, whether this polymorphism is associated with risk of myocardial infarction (MI) is uncertain.

METHODS AND RESULTS

In a prospective cohort of 14916 apparently healthy men enrolled in the Physicians' Health Study, allelic status for the TaqIB polymorphism in the CETP gene was determined among 384 participants who subsequently developed a first MI (cases) and among an equal number of age and smoking-matched participants who remained free of cardiovascular disease during follow-up (controls). Overall, the B2B2 genotype was present in 17% of the study participants and was associated with higher HDL cholesterol levels (mean mg/dl [+/- S.D.], 45 +/- 11 for the B1B1 genotype, 48 +/- 13 for the B1B2 genotype and 50 +/- 12 for the B2B2 genotype; P=0.01). However, the risk of developing MI did not differ significantly across these three genotypes. After adjustment for coronary risk factors (but not HDL), the relative risks for future MI were 1.12(95% CI 0.74-1.70) for the B1B2 genotype and 0.95(95% CI 0.54-1.66) for the B2B2 genotype, compared with the B1B1 genotype. In subgroup analysis of individuals with low HDL levels, B2B2 genotype appeared to have a lower risk of MI compared with the B1B1 genotype. However, participants with high HDL were at lower risk of developing MI regardless of their CETP genotype.

CONCLUSIONS

In this prospective study of apparently healthy middle-aged US men, carriers of the B2 allele of the TaqIB in the CETP gene had higher HDL concentrations, but did not have lower risk of MI.

CONDENSED ABSTRACT

In a cohort of apparently healthy middle-aged US men, the relation between CETP genotype and MI risk was prospectively examined in a nested case-control study. After adjusting for coronary risk factors (but not HDL), the 9-year risk of developing MI did not differ significantly by genotype. Comparing to the B1B1 genotype, the relative risks for future MI were 1.12 (95% CI 0.74-1.70) for the B1B2 genotype and 0.95 (95% CI 0.54-1.66) for the B2B2 genotype.

摘要

背景

胆固醇酯转运蛋白（CETP）编码基因的分子变异，如TaqIB多态性，与较高的血浆高密度脂蛋白（HDL）浓度相关。然而，这种多态性是否与心肌梗死（MI）风险相关尚不确定。

方法与结果

在参与医生健康研究的14916名表面健康男性的前瞻性队列中，在384名随后发生首次心肌梗死的参与者（病例组）以及相同数量的年龄和吸烟情况匹配、随访期间无心血管疾病的参与者（对照组）中，确定了CETP基因TaqIB多态性的等位基因状态。总体而言，17%的研究参与者存在B2B2基因型，且该基因型与较高的HDL胆固醇水平相关（B1B1基因型的平均mg/dl[±标准差]为45±11，B1B2基因型为48±13，B2B2基因型为50±12；P = 0.01）。然而，这三种基因型发生心肌梗死的风险并无显著差异。在对冠状动脉危险因素（但不包括HDL）进行调整后，与B1B1基因型相比，B1B2基因型未来发生心肌梗死的相对风险为1.12（95%可信区间0.74 - 1.70），B2B2基因型为0.95（95%可信区间0.54 - 1.66）。在HDL水平较低个体的亚组分析中，与B1B1基因型相比，B2B2基因型似乎发生心肌梗死的风险较低。然而，HDL水平高的参与者无论其CETP基因型如何，发生心肌梗死的风险都较低。

结论

在这项对表面健康的美国中年男性的前瞻性研究中，CETP基因TaqIB的B2等位基因携带者具有较高的HDL浓度，但心肌梗死风险并未降低。

摘要

在一组表面健康的美国中年男性队列中，通过巢式病例对照研究前瞻性地考察了CETP基因型与心肌梗死风险之间的关系。在对冠状动脉危险因素（但不包括HDL）进行调整后，9年内心肌梗死发生风险在各基因型之间无显著差异。与B1B1基因型相比，B1B2基因型未来发生心肌梗死的相对风险为1.12（95%可信区间0.74 - 1.7），B2B2基因型为0.95（95%可信区间0.54 - 1.66）。