血管紧张素转换酶插入/缺失多态性与血浆脂质反应及氟伐他汀治疗冠状动脉粥样硬化之间的相互作用：脂蛋白与冠状动脉粥样硬化研究

Interactions between angiotensin-I converting enzyme insertion/deletion polymorphism and response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin: the lipoprotein and coronary atherosclerosis study.

作者信息

Marian A J, Safavi F, Ferlic L, Dunn J K, Gotto A M, Ballantyne C M

机构信息

Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.

出版信息

J Am Coll Cardiol. 2000 Jan;35(1):89-95. doi: 10.1016/s0735-1097(99)00535-5.

DOI:10.1016/s0735-1097(99)00535-5

PMID:10636265

Abstract

OBJECTIVES

Our objectives were to determine whether angiotensin-1 converting enzyme (ACE) insertion/deletion (I/D) polymorphism was associated with the severity of coronary artery disease (CAD) and its progression/regression in response to fluvastatin therapy in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) population.

BACKGROUND

Genetic factors are involved in susceptibility to CAD. Angiotensin-1 converting enzyme I/D polymorphism, which accounts for half of the variance of plasma and tissue levels of ACE, has been implicated in susceptibility to CAD and myocardial infarction (MI).

METHODS

Angiotensin-1 converting enzyme genotypes were determined by polymerase chain reaction (PCR). Fasting plasma lipids were measured and quantitative coronary angiograms were obtained at baseline and 2.5 years following randomization to fluvastatin or placebo.

RESULTS

Ninety-one subjects had DD, 198 ID and 75 II genotypes. The mean blood pressure, minimum lumen diameter (MLD), number of coronary lesions and total occlusions were not significantly different at baseline or follow-up among the genotypes. There was a significant genotype-by-treatment interaction for total cholesterol (p = 0.018), low-density lipoprotein cholesterol (LDL-C) (p = 0.005) and apolipoprotein (apo) B (p = 0.045). In response to fluvastatin therapy, subjects with DD, compared with those with ID and II genotypes, had a greater reduction in total cholesterol (19% vs. 15% vs. 13%), LDL-C (31% vs. 25% vs. 21%) and apo B (23% vs. 15% vs. 12%). Definite progression was less (14%) and regression was more common (24%) in DD as compared with those with ID (32% and 17%) and II (33% and 3%) genotypes (p = 0.023). Changes in the mean MLD and lesion-specific MLD also followed the same trend.

CONCLUSIONS

Angiotensin-1 converting enzyme I/D polymorphism is associated with the response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin. Subjects with DD genotype had a greater reduction in LDL-C, a higher rate of regression and a lower rate of progression of CAD.

摘要

目的

我们的目的是在脂蛋白与冠状动脉粥样硬化研究（LCAS）人群中，确定血管紧张素转换酶（ACE）插入/缺失（I/D）多态性是否与冠状动脉疾病（CAD）的严重程度及其对氟伐他汀治疗的进展/逆转相关。

背景

遗传因素与CAD易感性有关。血管紧张素转换酶I/D多态性占血浆和组织中ACE水平差异的一半，与CAD和心肌梗死（MI）易感性有关。

方法

通过聚合酶链反应（PCR）确定血管紧张素转换酶基因型。测量空腹血脂，并在随机分组接受氟伐他汀或安慰剂治疗的基线和2.5年后获得定量冠状动脉造影。

结果

91名受试者为DD基因型，198名受试者为ID基因型，75名受试者为II基因型。各基因型在基线或随访时的平均血压、最小管腔直径（MLD）、冠状动脉病变数量和完全闭塞情况无显著差异。总胆固醇（p = 0.018）、低密度脂蛋白胆固醇（LDL-C）（p = 0.005）和载脂蛋白（apo）B（p = 0.045）存在显著的基因型与治疗交互作用。在接受氟伐他汀治疗后，与ID和II基因型受试者相比，DD基因型受试者的总胆固醇降低幅度更大（19% 对 15% 对 13%）、LDL-C降低幅度更大（31% 对 25% 对 21%）和apo B降低幅度更大（23% 对 15% 对 12%）。与ID（32%和17%）和II（33%和3%）基因型受试者相比，DD基因型受试者的明确进展较少（14%），而逆转更为常见（24%）（p = 0.023）。平均MLD和病变特异性MLD的变化也遵循相同趋势。