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Angiotensin-Converting Enzyme DD Polymorphism Is Associated With Poor Coronary Collateral Circulation in Patients With Coronary Artery Disease
  1. Koksal Ceyhan, MD*,
  2. Hasan Kadi, MD*,
  3. Atac Celik, MD*,
  4. Turgay Burucu, MD*,
  5. Fatih Koc, MD*,
  6. Erkan Sogut, MD,
  7. Semsettin Sahin, MD,
  8. Orhan Onalan, MD*
  1. From the Departments of *Cardiology and †Biochemistry, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey.
  1. Received June 29, 2011, and in revised form August 11, 2011.
  2. Accepted for publication September 21, 2011.
  3. Reprints: Koksal Ceyhan, MD, Department of Cardiology, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey. E-mail: kceyhan09{at}
  4. The authors have no conflict of interest.


Objectives Although association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and cardiovascular diseases was reported by many studies, the relation between ACE I/D polymorphism and coronary collateral circulation (CCC) has not been studied yet. The aim of the present study was to investigate a possible relationship between ACE I/D polymorphism and CCC.

Methods Patients who were subjected to coronary angiography in the 2006 to 2009 period and had at least a completely occluded major artery were included in this study. To classify collateral circulation, we used the Rentrop classification. Patients were classified as having poor CCC (Rentrop grades 0 to 1) or good CCC (Rentrop grades 2 to 3). Gene polymorphism was detected through the detailed melting curve analysis of polymerase chain reaction products after amplification using real-time polymerase chain reaction method and LightCycler 1.5 apparatus.

Results We prospectively studied 113 patients who had at least 1 totally occluded major epicardial coronary artery. Forty-seven patients had poor CCC and 67 patients had good CCC. There were no differences among groups in age, sex, risk factors, lipid profile, uses of cardiovascular drugs, and number of diseased vessels. Plasma ACE levels were significantly higher in poor CCC group (P < 0.001). The frequency of DD polymorphism was higher in the poor CCC group (P < 0.001). In allele frequency, we found that the frequency of the D allele was higher in poor CCC group than in the good CCC group (95% confidence interval [CI], 2.16–7.38; P < 0.001). Multiple regression analysis with CCC development as the dependent variable revealed that the presence of total occlusion of the left circumflex artery (95% CI, 1.29–6.6; P = 0.001), ACE DD genotype (95% CI, 2.55–12.79; P = 0.001), presence of diabetes (95% CI, 1.03–3.16; P = 0.005), and pulse pressure (95% CI, 1.04–1.56; P = 0.045) were independent determinants of poor coronary collateral development.

Conclusions This study showed that ACE DD polymorphism is associated with poor CCC. Poor collateral circulation in patients carrying the D allele may be associated with endothelial dysfunction and elevated blood ACE levels in these patients.

Key Words
  • collateral circulation
  • angiotensin-converting enzyme
  • gene polymorphism
  • coronary artery disease

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