Ruiz J, Blanché H, Cohen N, Velho G, Cambien F, Cohen D, Passa P, Froguel P
Centre d'Etude du Polymorphisme Humain, (Fondation Jean Dausset-CEPH), Paris, France.
Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3662-5. doi: 10.1073/pnas.91.9.3662.
Non-insulin-dependent diabetes mellitus (NIDDM) is considered a model of premature atherosclerosis with a strong genetic component. We have investigated the role of angiotensin-converting enzyme (ACE; EC 3.4.15.1) gene in 316 unrelated NIDDM individuals, 132 who had myocardial infarction or significant coronary stenoses and 184 with no history of coronary heart disease (CHD). A deletion-polymorphism in the ACE gene was recently reported to be associated with myocardial infarction especially in people classified as low risk. Here we report that the D allele of the ACE gene is a strong and independent risk factor for CHD in NIDDM patients. The D allele is associated with early-onset CHD in NIDDM, independently of hypertension and lipid values. A progressively increasing relative risk in individuals heterozygous and homozygous for the D allele was observed (odds ratios of 1.41 and 2.35, respectively; P < 0.007), suggesting a codominant effect on the cardiovascular risk. The percentage of CHD attributable to the ACE deletion allele was 24% in this NIDDM population. Identification of NIDDM patients carrying this putative CHD-susceptibility genotype would help early detection and treatment of CHD.
非胰岛素依赖型糖尿病（NIDDM）被认为是一种具有强烈遗传成分的早发性动脉粥样硬化模型。我们研究了血管紧张素转换酶（ACE；EC 3.4.15.1）基因在316名无亲缘关系的NIDDM患者中的作用，其中132人患有心肌梗死或严重冠状动脉狭窄，184人无冠心病（CHD）病史。最近有报道称，ACE基因中的一种缺失多态性与心肌梗死有关，尤其是在被归类为低风险的人群中。在此我们报告，ACE基因的D等位基因是NIDDM患者患CHD的一个强烈且独立的风险因素。D等位基因与NIDDM患者的早发性CHD相关，与高血压和血脂水平无关。观察到D等位基因杂合子和纯合子个体的相对风险逐渐增加（优势比分别为1.41和2.35；P < 0.007），表明对心血管风险有共显性效应。在这个NIDDM人群中，归因于ACE缺失等位基因的CHD百分比为24%。识别携带这种假定的CHD易感性基因型的NIDDM患者将有助于CHD的早期检测和治疗。
