Sekuri Cevad, Cam F Sirri, Ercan Ertugrul, Tengiz Istemihan, Sagcan Abdi, Eser Erhan, Berdeli Afig, Akin Mustafa
Department of Cardiology, Kent Hospital, Izmir, Turkey.
J Renin Angiotensin Aldosterone Syst. 2005 Mar;6(1):38-42. doi: 10.3317/jraas.2005.005.
Experimental and clinical studies demonstrated that the renin-angiotensin system (RAS) affects the pathogenesis of atherosclerosis and prognosis of coronary heart disease (CHD). The aim of this study was to investigate the genotype distribution and the allele frequencies of three RAS genes polymorphisms and their effects on premature CHD in a Turkish population.
One-hundred and fifteen Turkish patients with premature CHD and 128 controls were included into the study. Angiotensin-converting enzyme (ACE), angiotensin II type 1 (AT1) receptor and angiotensinogen (AGT) gene polymorphisms were analysed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).
The patients group showed an increased frequency of the ACE D allele compared with controls (65% vs. 35%, p = 0.0001). There was a significant association between the DD genotype and premature CHD (ACE DD vs. ID and II; odds ratio [OR] = 2.82 [CI 95% 1.33 2.91, p = 0.002]). Also, we observed increased premature CHD risk associated with higher frequencies of the AGT MM genotype in patients when compared with controls (AGT MM vs. TT and MT, OR = 1.92 [CI 95% 1.11-3.33, p = 0.018]). We found a significant association between AT1-receptor AA genotype and decreased risk of premature CHD (AT1R AA vs. AC and CC, OR = 0.57[CI 95% 0.34-0.95, p = 0.03]).
We demonstrated that increased premature CHD risk is associated with higher frequencies of the ACE DD and AGT MM genotypes. These findings indicate a synergistic contribution of ACE DD and AGT MM polymorphisms to the development of premature CHD. Also, our results suggest that family history, smoking, diabetes, hypertension, obesity and ACE DD genotype were independent risk factors for premature CHD.
实验和临床研究表明，肾素-血管紧张素系统（RAS）影响动脉粥样硬化的发病机制和冠心病（CHD）的预后。本研究的目的是调查土耳其人群中三种RAS基因多态性的基因型分布和等位基因频率及其对早发性冠心病的影响。
115例早发性冠心病土耳其患者和128例对照纳入本研究。采用聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）分析血管紧张素转换酶（ACE）、血管紧张素II 1型（AT1）受体和血管紧张素原（AGT）基因多态性。
与对照组相比，患者组ACE D等位基因频率增加（65%对35%，p = 0.0001）。DD基因型与早发性冠心病之间存在显著关联（ACE DD与ID和II相比；比值比[OR]=2.82[95%CI 1.33-2.91，p = 0.002]）。此外，与对照组相比，我们观察到患者中AGT MM基因型频率较高与早发性冠心病风险增加相关（AGT MM与TT和MT相比，OR = 1.92[95%CI 1.11-3.33，p = 0.018]）。我们发现AT1受体AA基因型与早发性冠心病风险降低之间存在显著关联（AT1R AA与AC和CC相比，OR = 0.57[95%CI 0.34-0.95，p = 0.03]）。
我们证明早发性冠心病风险增加与ACE DD和AGT MM基因型的较高频率相关。这些发现表明ACE DD和AGT MM多态性对早发性冠心病的发展有协同作用。此外，我们的结果表明家族史、吸烟、糖尿病、高血压、肥胖和ACE DD基因型是早发性冠心病的独立危险因素。
