A promoter variant of the heme oxygenase-1 gene may reduce the incidence of ischemic heart disease in Japanese
A promoter variant of the heme oxygenase-1 gene may reduce the incidence of ischemic heart disease in Japanese
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DOI：
10.1016/j.atherosclerosis.2003.11.021
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发表时间：
2004-04-01
期刊：
影响因子：
5.3
通讯作者：
Iwai, N
中科院分区：
文献类型：
--
作者：
Ono, K;Goto, Y;Iwai, N
血红素加氧酶-1 （HO-1）被认为具有抗动脉粥样硬化的特性。本研究旨在探讨HO-1基因（HMOX1）与缺血性心脏病之间的关系。研究人群包括1972名对照组和597名缺血性心脏病患者（心肌梗死（MI） n = 393, HMOX1 n = 204）。对照对象从Suita研究中连续选择，这是一个代表日本普通人群的流行病学队列。缺血性心脏病患者从国家心血管中心（NCVC）门诊招募。我们对HMOX1进行了测序，在启动子区域发现了一个T(-413) a多态性。多因素logistic分析提示，T(-413)A （TA + 7-T/AA）多态性、性别、吸烟习惯、糖尿病和BMI对缺血性心脏病的发生有影响。MI和AP的TA + TT等位基因比值比分别为1.42 （P = 0.0468, 95%可信区间为0.01 ~ 0.35）和1.86 （P = 0.0096, 95%可信区间为0.08 ~ 0.55）。荧光素酶报告子实验表明，A等位基因启动子的活性显著高于T等位基因启动子。HMOX1的AA基因型降低了缺血性心脏病的发病率，可能与HMOX1的高表达水平有关。2004爱思唯尔爱尔兰有限公司版权所有。
Heme oxygenase-1 (HO-1) has been suggested to have antiatherogenic properties. This study was designed to examine the relationship between the HO-1 gene (HMOX1) and ischemic heart disease. The study Population consisted of 1972 control subjects and 597 subjects with ischemic heart disease (myocardial infarction (MI) n = 393, HMOX1 n = 204). The control subjects were consecutively selected from the Suita study, an epidemiological cohort representing the general population in Japan. Patients with ischemic heart disease were recruited from the outpatient clinic of the National Cardiovascular Center (NCVC). We sequenced HMOX1 and found a T(-413)A polymorphisin in the promoter region. Multiple logistic analyses indicated that the T(-413)A (TA + 7-T/AA) polymorphism, sex, smoking habit, DM and BMI affected the occurrence of ischemic heart disease. The odds ratios of the TA + TT allele for MI and AP were 1.42 (P = 0.0468, 95% confidence interval: 0.01-0.35) and 1.86 (P = 0.0096, 95% confidence interval: 0.08-0.55), respectively. Luciferase reporter assay indicated that the A allele promoter had significantly higher activity than the T allele promoter. The AA genotype of HMOX1 reduced the incidence of ischemic heart disease, possibly due to the high expression level of HMOX1. (C) 2004 Elsevier Ireland Ltd. All rights reserved.