INSERTION/DELETION POLYMORPHISM OF THE ANGIOTENSIN-CONVERTING ENZYME GENE IS STRONGLY ASSOCIATED WITH CORONARY HEART-DISEASE IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS
INSERTION/DELETION POLYMORPHISM OF THE ANGIOTENSIN-CONVERTING ENZYME GENE IS STRONGLY ASSOCIATED WITH CORONARY HEART-DISEASE IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS
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DOI：
10.1073/pnas.91.9.3662
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发表时间：
1994-04-26
影响因子：
11.1
通讯作者：
FROGUEL, P
中科院分区：
文献类型：
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作者：
RUIZ, J;BLANCHE, H;FROGUEL, P
非胰岛素依赖型糖尿病(NIDDM)被认为是一种具有很强遗传成分的过早动脉粥样硬化模型。我们研究了血管紧张素转换酶(ACE；EC 3.4.15.1)基因在316例无血缘关系的NIDDM患者中的作用，其中132例有心肌梗死或明显冠状动脉狭窄，184例无冠心病病史。血管紧张素转换酶基因的缺失-多态最近被报道与心肌梗死有关，特别是在被归类为低风险人群中。在此，我们报道血管紧张素转换酶基因D等位基因是NIDDM患者CHD的独立危险因素。D等位基因与NIDDM的早发性CHD相关，与高血压和血脂无关。在D等位基因杂合子和纯合子个体中，观察到相对风险逐渐增加(优势比分别为1.41和2.35；P<；0.007)，表明对心血管风险存在共显性效应。在该NIDDM人群中，可归因于ACE缺失等位基因的CHD百分比为24%。NIDDM患者携带此推测的CHD易感基因将有助于CHD的早期发现和治疗。
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.