The relationship between coronary artery ectasia and PAİ-1 4G/5G gene polymorphi̇sms

Introduction and Aim: Cardiovascular diseases are among the most important causes of mortality and morbidity in our country as well as all over the world. Coronary artery disease occupies the most important place among cardiovascular diseases. CAD occurs as a result of narrowing or complete occlusion of the epicardial coronary arteries. CAD is a serious disease that can cause deterioration in cardiac functions, development of heart failure and death in patients, and despite all the treatment techniques developed today, the desired satisfactory results cannot be obtained in most patients. Another pathology related to coronary artery is coronary artery ectasia.Coronary artery ectasia is a pathology with abnormal enlargement of the coronary epicardial arteries.Although CAE is clinically asymptomatic in some patients, it causes the development of angina and palpitations in some patients, and in some patients it may lead to fatal events such as myocardial infarction due to coronary thromboembolism.Studies show that coronary artery ectasia has similar pathophysiological mechanisms with CAD and its association with coronary artery disease is common.In addition, it has been reported that the risk factors valid for atherosclerosis are also valid for patients with CAE.However, many patients with CAE only have ectasia without any signs of coronary artery disease. This group of patients is defined as isolated coronary artery ectasia (ICAE). Although many environmental factors have been suggested in the etiology of ICAE, it is suspected that genetic factors also play a role. It has been proven in many studies that genetic factors besides environmental factors have an important effect on the etiology of cardiovascular diseases. As in the pathogenesis of other cardiovascular diseases, the role of genetic factors together with environmental factors is undeniably high in the development of CAE. However, the genetic mechanisms that play a role in the formation of CAE are not yet fully understood. When the histopathological structure of CAE is examined; It has been determined that the coronary artery wall, especially the tunica media layer, has lost its strength and degenerated. Vasovasorum has a very important role in maintaining the strength and feeding of the artery wall. The homeostatic system must work properly in order for the tunika media layer to be fed healthily by vasovasorums. Therefore, it can be thought that coagulation and fibrinolytic system vii disorders play an important role in the process of CAE formation. The plasminogen activator system plays a central role in the dynamic balance between these two systems. Plasminogen activator system consists of different proteins and enzymes, including tissue-plasminogen activator (t-PA) and plasminogen activator-1 (PAI-1). Plasmin is the main enzyme in the fibrinolytic system and dissolution of the fibrin clot. Conversion of plasminogen to plasmin is catalyzed by t-PA and inhibited by PAI-1. Therefore, high PAI- 1 activity causes a decrease in fibrinolytic system activity. In addition, high PAI-1 activity plays an important role in the emergence of pathologies such as atherosclerosis, thromboembolic diseases and stroke. Various polymorphisms have been identified that affect plasma PAI-1 levels, such as the -675 4G / 5G insertion / deletion polymorphism and the -844 G / A single nucleotide polymorphism. In this study, we investigated the effect of PAI-1 4G / 5G polymorphism, which has been shown to play a role in cardiovascular diseases in previous studies, on the formation of coner artery ectasia. Material and Methods: The study is conducted in Rize Recep Tayyip Erdogan University Education Research Hospital as a cross section observational study. The diagnosis of coronary artery ectasia was defined as dilatation of an arterial segment to a diameter at least 1.5 times that of the adjacent normal coronary artery. The diagnosis of CAE was made in the patients by conventional coronary angiography. 53 patients with coronary artery ectasia and 52 age-matched control patients with normal coronary arteries were included in the study. Demographic characteristics, clinical findings, biochemical parameters, and presence of cardiovascular disease risk factors of each individual in the patient and control groups were questioned. DNA genotype analysis of the patients was performed. For DNA genotype analysis, genomic DNAs of individuals were isolated from peripheral whole blood leukocytes. Genotype analysis for the variant of DNA samples was performed by real-time polymerase chain reaction (RT-PCR) based on Taqman chemistry. The frequency of PAI-1 4G / 5G polymorphism and clinical findings, certain blood serum parameters, demographic characteristics of the patients, presence of risk factors were statistically compared in the groups. Results: Types of coronary artery ectasia, type 1 (n =17), type 2 (n =7), type 3(n=7), type4 (n =22) groups were compared among themselves and with the control group viii in terms of genotype frequency. A statistically significant difference was not found between the CAE and control groups in terms of the distribution of 4G / 5G polymorphism. We found no difference in the incidence of polymorphism among CAE subgroups. Conclusion: These results suggest that there is not a significant relationship between 4G / 5G polymorphism and CAE risk. However the PAI-1 gene polymorphism, together with certain other environmental and genetic factors, may be playing a role in the risk of developing CAE.