Molecular Diagnostic Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Mol Biol Rep. 2012 Mar;39(3):2723-31. doi: 10.1007/s11033-011-1027-4. Epub 2011 Jun 17.
We have previously shown that angiotensin-converting enzyme (ACE) gene D allele is an independent risk factor for early onset coronary artery disease (CAD). Little is known about the concomitant presence of the ACE gene D allele and paraoxonase (PON1) codon 192 arginine (Arg) on the severity of CAD. Regarding the high rate of CAD among Iranians the aim of present study was to examine the hypothesis of synergistic effects between ACE-D and PON1-Arg alleles on predisposition and the severity of CAD in our population. The PON1 192 and ACE insertion/deletion (I/D) genotypes were detected by PCR-RFLP and PCR, respectively in 414 individuals undergoing their first coronary angiography. Patients were placed into one of two groups: CAD and control without CAD or diabetes. We mentioned the synergistic effects of both genes and not ACE gene alone is a risk factor for CAD. We found that PON1 Arg 192 and ACE D allele act synergistically to increase the risk of CAD (OR 1.3, P = 0.044). Our results showed a significant correlation between the possession of both PON1 192 Arg and the ACE D allele and the extent of CAD in CAD patients and CAD subjects without diabetes, represented by the increased frequency of three-vessel disease with OR 2.7, P = 0.046; χ(2) = 4, P = 0.046 and OR 2.4, P = 0.051; χ(2) = 3.8, P = 0.051, respectively. We found that PON1 Arg 192 and ACE D alleles act synergistically to increase the risk of CAD in CAD patients and CAD subjects without diabetes from west of Iran, who have high frequency of three-vessel disease. Our data suggest that PON1 192 Arg and the ACE D allele in combination with each other can be important independent risk factor for severity of CAD in patients carrying both PON1 192 Arg and the ACE D allele in a west population of Iran.
我们之前已经表明，血管紧张素转换酶（ACE）基因 D 等位基因是早发性冠心病（CAD）的独立危险因素。对于 ACE 基因 D 等位基因和对氧磷酶（PON1）密码子 192 精氨酸（Arg）同时存在与 CAD 严重程度的关系知之甚少。鉴于伊朗人中 CAD 的高发病率，本研究旨在检验 ACE-D 和 PON1-Arg 等位基因在我们人群中对 CAD 易感性和严重程度的协同作用假设。通过 PCR-RFLP 和 PCR 分别检测了 PON1 192 和 ACE 插入/缺失（I/D）基因型，共对 414 名接受首次冠状动脉造影的个体进行了检测。患者分为两组：CAD 组和无 CAD 或糖尿病的对照组。我们提到了这两个基因的协同作用，而不仅仅是 ACE 基因是 CAD 的危险因素。我们发现 PON1 Arg 192 和 ACE D 等位基因协同作用增加 CAD 的风险（OR 1.3，P = 0.044）。我们的结果表明，在 CAD 患者和无糖尿病的 CAD 患者中，同时携带 PON1 192 Arg 和 ACE D 等位基因与 CAD 的严重程度之间存在显著相关性，表现为三血管疾病的频率增加，OR 为 2.7，P = 0.046；χ² = 4，P = 0.046 和 OR 为 2.4，P = 0.051；χ² = 3.8，P = 0.051。我们发现，在来自伊朗西部的 CAD 患者和无糖尿病的 CAD 患者中，PON1 Arg 192 和 ACE D 等位基因协同作用增加 CAD 的风险，这些患者的三血管疾病频率较高。我们的数据表明，PON1 192 Arg 和 ACE D 等位基因相互作用可以成为伊朗西部人群中同时携带 PON1 192 Arg 和 ACE D 等位基因的 CAD 患者严重程度的重要独立危险因素。
