Pathophysiology and natural history 85 Endothelial nitric oxide synthase gene (T-786C) polymorphism in patients with slow coronary flow Zekeriya Nurkalem, Burak Tangurek, Ertugrul Zencirci, Ahmet T. Alper, Huseyin Aksu, Betul Erer, Sevket Gorgulu, Figen Ciloglu and Mehmet Eren Objectives In this study, we aimed to investigate the relationship between T-786C polymorphism of the endothelial nitric oxide synthase (eNOS) gene and slow coronary flow (SCF). Study design A total of 56 patients with SCF but otherwise normal coronary arteries (mean age 48 ± 9 years) and 37 controls with normal coronary angiograms (mean age 50 ± 12 years) were enrolled in the study. Screening for the eNOS T-786C polymorphism was performed by restriction fragment length polymorphism methodology. Results In normal coronary artery and SCF groups, TT genotype frequency was 23 (62.2%) versus 22 (39.3%), TC heterozygote genotype frequency was 11 (29.7%) versus 30 (53.6%), and CC homozygote genotype frequency was 3 (8.1%) versus 4 (7.1%), respectively (P = 0.07). In dominant model statistical analysis, total CC and CT genotype frequency in control and study groups was found to be 14 (37.3%) versus 34 (60.7%), respectively (P = 0.025). A positive correlation was found between the mean thrombolysis in myocardial infarction frame count and C allele in patients with SCF (r = 0.21, P = 0.043). Conclusion We concluded that the T-786C polymorphism of eNOS gene might be a risk factor for the SCF. Coron Artery Dis 19:85–88  c 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins. Coronary Artery Disease 2008, 19:85–88 Keywords: endothelial nitric oxide synthase gene, nitric oxide, slow coronary flow, T-786C polymorphism Siyami Ersek Cardiovascular and Thoracic Surgery Center, Training and Research Hospital, Istanbul, Turkey Correspondence to Dr Zekeriya Nurkalem, MD, Siyami Ersek Cardiovascular and Thoracic Surgery Center, Training and Research Hospital, Tibbiye C. No. 18 Haydarpasa, Istanbul, Turkey Tel: + 902163499120; e-mail: zeknurkalem@yahoo.com Received 7 September 2007 Revised 22 November 2007 Accepted 5 December 2007 Introduction The endothelium-derived nitric oxide (NO) is synthe- sized from the substrate L-arginine via endothelial NO synthase (eNOS) and plays a crucial role in regulating a wide spectrum of functions in the cardiovascular system, including vasorelaxation, inhibition of leukocyte- endothelial adhesion, vascular smooth muscle cell migration and proliferation, as well as platelet aggregation. Experi- mental and clinical studies provide evidence that defects of endothelial NO function cause endothelial dysfunction [1–4]. The T-786C variation in the 5 0 flanking region of the eNOS gene was originally reported by Nakayama et al. [5] to be associated with coronary vasospasm by affecting eNOS expression, supporting the hypothesis that in many carriers of the mutant allele the L-arginine-NO pathway does not function properly leading to endothelial dysfunction. This variant, which results in a significant reduction in the eNOS gene promoter activity, causes a reduction in NO levels and has been associated with an increased risk for coronary spasm [6]. Slow coronary flow (SCF) is a well-recognized clinical entity, characterized by delayed opacification of coronary arteries in the presence of normal coronary angiogram [7]. Many etiological factors such as microvascular and endothelial dysfunction have been implicated [8–12]. Along with impaired endothelial function, reduced plasma level of NO has also been demonstrated in some studies involving SCF [8,11,12]. Therefore, we under- took this study to investigate whether the eNOS T-786C polymorphism is related to SCF. Materials and methods Study population We selected a total of 56 patients with SCF and otherwise normal coronary arteries (mean age 48 ± 9 years) (SCF group) and 37 patients with normal coronary angiograms (mean age 50 ± 12 years) (control group), among 5940 consecutive patients who underwent their first diagnostic coronary angiography for the evaluation of angina in our center between December 2004 and May 2005. These patients were then prospectively evaluated to determine the relationship between T-786C mutation of eNOS gene and SCF. The patients were defined as hypertensive if their blood pressure was greater than 140/90 mmHg or if they were receiving any antihypertensive medication. Diabetes mellitus was defined if the individuals had a previous diagnosis, a history of antidiabetic medication usage or fasting glucose levels above 126 mg/dl. The smoking status was classified as smokers or those who 0954-6928  c 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins