Ishigami T, Umemura S, Iwamoto T, Tamura K, Hibi K, Yamaguchi S, Nyuui N, Kimura K, Miyazaki N, Ishii M
Second Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Circulation. 1995 Feb 15;91(4):951-4. doi: 10.1161/01.cir.91.4.951.
A positive association was previously reported between angiotensin-converting enzyme (ACE) gene polymorphism and several cardiovascular diseases, such as myocardial infarction, left ventricular hypertrophy, and restenosis after percutaneous transluminal coronary angioplasty. Plasma ACE activity and carotid-wall thickening measured by ultrasonography were related, and it was postulated that long-term exposure to high levels of plasma ACE could be involved in structural changes of the arterial wall. In addition, angiotensinogen gene mutation was recently reported to be associated with essential hypertension and preeclampsia. There exists a possibility that the renin-angiotensin system plays an important role in the progress of cardiovascular diseases in humans. Therefore, we examined the association between the molecular variant of the angiotensin gene and coronary atherosclerosis.
This study included 82 patients who had coronary atherosclerosis and 160 control subjects; all study participants were Japanese. All patients with coronary atherosclerosis had at least one coronary artery with > 25% luminal diameter obstruction on average according to multiple coronary angiographic views. Angiotensinogen gene molecular variants were designated AA, Aa, and aa. The a allele indicated thymine-cytosine transition at nucleotide 704 in exon 2. Genomic DNA was extracted from peripheral blood leukocytes. Polymerase chain reaction was performed to amplify the concerned region of the angiotensinogen gene. After restriction enzyme digestion, it was possible to distinguish the molecular variant of the angiotensinogen gene. The frequencies of these genotypes were 7.3%, 26.8%, and 65.9% in the patients and 18.8%, 31.9%, and 49.3% in the control subjects for the AA, Aa, and aa alleles, respectively. There was an excess in the a allele among patients (P < .01).
We found a significant association between coronary atherosclerosis and a molecular variant of the angiotensin gene. The results suggested that the molecular variant of the angiotensinogen gene could be a new risk factor for coronary atherosclerosis.
先前有报道称血管紧张素转换酶（ACE）基因多态性与多种心血管疾病存在正相关，如心肌梗死、左心室肥厚以及经皮腔内冠状动脉成形术后再狭窄。通过超声检查测得的血浆ACE活性与颈动脉壁增厚有关，据推测长期暴露于高水平的血浆ACE可能参与动脉壁的结构改变。此外，最近有报道称血管紧张素原基因突变与原发性高血压和先兆子痫有关。肾素 - 血管紧张素系统有可能在人类心血管疾病的进展中起重要作用。因此，我们研究了血管紧张素基因的分子变异与冠状动脉粥样硬化之间的关联。
本研究纳入了82例患有冠状动脉粥样硬化的患者和160例对照者；所有研究参与者均为日本人。根据多个冠状动脉造影视图，所有患有冠状动脉粥样硬化的患者平均至少有一支冠状动脉的管腔直径阻塞>25%。血管紧张素原基因分子变异被指定为AA、Aa和aa。a等位基因表示外显子2中核苷酸704处的胸腺嘧啶 - 胞嘧啶转换。从外周血白细胞中提取基因组DNA。进行聚合酶链反应以扩增血管紧张素原基因的相关区域。经过限制性酶切后，可以区分血管紧张素原基因的分子变异。对于AA、Aa和aa等位基因，这些基因型的频率在患者中分别为7.3%、26.8%和65.9%，在对照者中分别为18.8%、31.9%和49.3%。患者中a等位基因过多（P < .01）。
我们发现冠状动脉粥样硬化与血管紧张素基因的分子变异之间存在显著关联。结果表明血管紧张素原基因的分子变异可能是冠状动脉粥样硬化的一个新的危险因素。
