Winkelmann B R, Russ A P, Nauck M, Klein B, Böhm B O, Maier V, Zotz R, Matheis G, Wolf A, Wieland H, Gross W, Galton D J, März W
Department of Cardiology, Ludwigshafen Heart Center, Frankfurt, Germany.
Am Heart J. 1999 Apr;137(4 Pt 1):698-705. doi: 10.1016/s0002-8703(99)70226-7.
Genes encoding components of the renin-angiotensin system have been associated with elevated blood pressure (BP) and an increased risk of coronary artery disease. To explore the role of the angiotensinogen (AGT) gene in coronary atherosclerosis and thrombosis, we studied the effect of the AGT M235T gene variant on plasma AGT levels and BP in patients with coronary artery disease and in the subgroup of survivors of myocardial infarction as compared with angiographically defined control subjects.
This was a case-control study of 301 white male subjects examined at Frankfurt University medical center. Plasma AGT levels increased stepwise according to the number of T235 alleles present (no T235 allele, 14.8 +/- 3.9 nmol/L; 1 allele, 15.7 +/- 5.1 nmol/L; 2 alleles, 17.3 +/- 4.7 nmol/L; P =.006). In a multivariate model, circulating AGT emerged as the most important predictor of diastolic pressure (P =.001). In addition, AGT M235T gene polymorphism remained a significant predictor of diastolic BP in a multivariate model adjusted for age, body mass index, fasting glucose, apolipoprotein B, presence of coronary artery disease, and treatment with antihypertensive agents ( P <.05). Finally, homozygosity for T235 was associated with increased univariate risk of coronary artery disease and myocardial infarction (odds ratio estimates 1.5; 95% confidence intervals 1.1 to 2.1, P =.03, and 1.0 to 2.1, P =.05, respectively).
The significant relations observed between the AGT M235T variant, its protein product, and the cardiovascular disease phenotypes provide evidence for a possible role of elevated circulating AGT in the pathogenesis of coronary artery disease.
编码肾素 - 血管紧张素系统成分的基因与血压升高及冠状动脉疾病风险增加有关。为探究血管紧张素原（AGT）基因在冠状动脉粥样硬化和血栓形成中的作用，我们研究了AGT M235T基因变异对冠状动脉疾病患者及心肌梗死存活者亚组血浆AGT水平和血压的影响，并与血管造影确定的对照受试者进行比较。
这是一项对法兰克福大学医学中心检查的301名白人男性受试者进行的病例对照研究。血浆AGT水平根据存在的T235等位基因数量逐步升高（无T235等位基因，14.8±3.9 nmol/L；1个等位基因，15.7±5.1 nmol/L；2个等位基因，17.3±4.7 nmol/L；P = 0.006）。在多变量模型中，循环AGT成为舒张压的最重要预测因子（P = 0.001）。此外，在根据年龄、体重指数、空腹血糖、载脂蛋白B、冠状动脉疾病的存在及抗高血压药物治疗进行调整的多变量模型中，AGT M235T基因多态性仍然是舒张压的显著预测因子（P < 0.05）。最后，T235纯合子与冠状动脉疾病和心肌梗死的单变量风险增加相关（优势比估计值分别为1.5；95%置信区间1.1至2.1，P = 0.03，以及1.0至2.1，P = 0.05）。
观察到的AGT M235T变异、其蛋白产物与心血管疾病表型之间的显著关系为循环AGT升高在冠状动脉疾病发病机制中可能发挥的作用提供了证据。
