The angiotensin‐converting enzyme (ACE) genetic polymorphism: its relationship with plasma ACE level and myocardial infarction
The angiotensin‐converting enzyme (ACE) genetic polymorphism: its relationship with plasma ACE level and myocardial infarction
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DOI：
10.1111/j.1399-0004.1994.tb04210.x
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发表时间：
1994-07
影响因子：
3.5
通讯作者：
F. Cambien
中科院分区：
文献类型：
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作者：
F. Cambien
血管紧张素转换酶（ACE）是血管紧张素II产生和缓激肽降解的关键因素，缓激肽是参与血管生理学的两种重要肽。人血浆和细胞ACE水平受ACE基因插入（I）/缺失（D）多态性（ACE I/D多态性）的影响。D等位基因在高加索人群中的频率约为0.53，并且与较高水平的ACE共显性相关。我们在一项大型多中心病例对照研究（ECTIM研究）中研究了这种多态性，发现D等位基因与对照组中父母的致死性心肌梗死（MI）病史相关，并且在男性MI患者中比对照组更常见。这种病例对照差异与等位基因D对MI风险的共显性效应相一致，DD与II的相对风险为1.57，ID与II的相对风险为1.26（趋势检验p < 0.003）。在MI低风险受试者中（血浆ApoB < 1.25 g/l和体重指数< 26 kg/m2），DD与ID + II的相对风险为2.7（p < 0.0005）。研究中包括的四个人群的结果非常一致。在一项家族研究中，使用连锁分离分析，我们发现ACE I/D多态性是一种未知功能多态性（ACE S/s）的标志物，该多态性似乎是MI的一个新的独立危险因素。
The angiotensin‐converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin, two important peptides involved in vascular physiology. Plasma and cellular ACE levels in humans are influenced by an insertion (I)/deletion (D) polymorphism of the ACE gene, the ACE I/D polymorphism. The D allele has a frequency of approximately 0.53 in Caucasian populations and is codominantly associated with higher levels of ACE. We have studied this polymorphism in a large multicenter case‐control study (the ECTIM study) and found that the D allele was associated with a parental history of fatal myocardial infarction (MI) in the controls and was more frequent in male patients with MI than in controls. This case‐control difference was compatible with a codominant effect of allele D on the risk of MI with relative risks of 1.57 for DD vs II and 1.26 for ID vs II (test for trend p < 0.003). In subjects at low risk of MI (plasma ApoB < 1.25 g/1 and body mass index < 26 kg/m2), the relative risk of DD vs ID + II was 2.7 (p < 0.0005). The results were very homogeneous in the four populations included in the study. In a family study, using linkage‐segregation analysis, we have shown that the ACE I/D polymorphism is a marker for an unknown functional polymorphism (ACE S/s) which appears to be a new independent risk factor for MI.