Kaneda Hideaki, Ohno Minoru, Taguchi Junichi, Togo Masako, Hashimoto Hideki, Ogasawara Ken, Aizawa Tadanori, Ishizaka Nobukazu, Nagai Ryozo
Department of Cardiovascular Medicine, The University of Tokyo, Graduate School of Medicine, Tokyo, Japan.
Arterioscler Thromb Vasc Biol. 2002 Oct 1;22(10):1680-5. doi: 10.1161/01.atv.0000033515.96747.6f.
Heme oxygenase (HO) is important in the defense against oxidative stress and as a factor in an antiatherogenic mechanism. Compared with long (GT)(n) repeats, short (GT)(n) repeats in the human HO-1 gene promoter were shown to have higher transcriptional activity in response to oxidative stress. There is a strong link between oxidative stress and the pathogenesis of coronary artery disease (CAD).
We screened the allelic frequencies of (GT)(n) repeats in the HO-1 gene promoter in 577 patients who underwent coronary angiography. Because the distribution of numbers of (GT)(n) repeats was bimodal, we divided the alleles into 2 subclasses: class S included shorter (<27) repeats, and class L included longer (> or =27) repeats. Multivariate logistic regression models including standard coronary risk factors revealed that the genotypes were significantly related to CAD status in hypercholesterolemic, diabetic patients or in smokers. In this study, the patients with shorter GT repeats were less likely to have CAD.
Length polymorphism in the HO-1 gene promoter is related to CAD susceptibility in Japanese people who also have coronary risk factors such as hypercholesterolemia, diabetes, and smoking. HO-1 may play an antiatherogenic role in Japanese patients with these coronary risk factors.
血红素加氧酶（HO）在抵御氧化应激及作为抗动脉粥样硬化机制的一个因素方面很重要。与长（GT）（n）重复序列相比，人类HO-1基因启动子中的短（GT）（n）重复序列在氧化应激反应中表现出更高的转录活性。氧化应激与冠状动脉疾病（CAD）的发病机制之间存在紧密联系。
我们在577例接受冠状动脉造影的患者中筛查了HO-1基因启动子中（GT）（n）重复序列的等位基因频率。由于（GT）（n）重复序列数量的分布呈双峰型，我们将等位基因分为2个亚类：S类包括较短（<27）的重复序列，L类包括较长（≥27）的重复序列。包含标准冠状动脉危险因素的多变量逻辑回归模型显示，在高胆固醇血症患者、糖尿病患者或吸烟者中，基因型与CAD状态显著相关。在本研究中，GT重复序列较短的患者患CAD的可能性较小。
HO-1基因启动子的长度多态性与具有高胆固醇血症糖尿病和吸烟等冠状动脉危险因素的日本人的CAD易感性相关。HO-1可能在患有这些冠状动脉危险因素的日本患者中发挥抗动脉粥样硬化作用。
