Nergiz Domaniç

DNA repair gene XRCC1 and XPD polymorphisms and their association with coronary artery disease risks and micronucleus frequency

Coronary artery disease (CAD) is a multifactorial process that appears to be caused by the interaction of environmental risk factors with multiple predisposing genes. In this study, we investigated the effects of the XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on the presence and the severity of CAD. We also investigated the presence of DNA damage in the peripheral lymphocytes of patients with CAD by using the micronucleus (MN) test and the effect of XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on this damage. The study population consisted of 147 patients with angiographically documented CAD and 48 healthy controls. No association between XPD Lys751Gln or XRCC1 Arg399Gln polymorphisms and the presence or the severity of CAD was observed. On the other hand, a significantly higher frequency of MN was observed in CAD patients compared with controls (5.7 ± 1.9 vs 5.0 ± 2.1, respectively, P = 0.018). We found an elevated frequency of MN in CAD patients with the XPD 751Gln allele (Gln/Gln genotype) or the XRCC1 399Gln (Arg/Gln or Gln/Gln genotypes) allele compared with the XPD 751Lys (Lys/Lys genotype) allele or XRCC1 399 Arg (Arg /Arg genotype) allele, respectively. These preliminary results suggest that XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms may not be a significant risk factor for developing CAD. In addition, our results indicate that the MN frequency is associated with presence, but not severity, of CAD and is related to the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms, suggesting an elevated frequency of MN in CAD patients with the XPD 751Gln or XRCC1 399Gln alleles.

Plasma vitronectin levels in patients with coronary atherosclerosis are increased and correlate with extent of disease.

AbstractBackground: Acute thrombosis after atherosclerotic plaques disruption is a major complication of primary atherosclerosis, leading to acute ischemic syndromes and atherosclerotic proression. Vitronectin (VN) is multifunctional glycoprotein in blood and in the extracellular matrix. It binds glycosaminoglycans, collagen, plasminogen and urokinase receptor. VN stabilizes the inhibitory confirmation of plasminogen activation inhibitor-1 (PAI-1). Vitronectin may control the clerance of vascular thrombi by binding and stabilizing PAI-1, a key regulator of fibrinolysis. Therefore, VN is generally regarded as a cofactor for PAI-1 activity. On the other hand vitronectin binds to platelet glycoproteins may mediate platelet adhesion and aggregation at sites of vascular injury. Previous studies showed that anti-VN antibodies inhibit platelet aggregation in vitro, suggesting that vitronectin contributes to platelet accumulation at sites of vascular injury. In this study; we investigated the levels of plasma vitronectin in patients with Coronary Artery Disease (CAD) and control group. Methods: The patient group was divided into four subgroups: patients with no, single, double and triple vessel disease according to their angiography results. ELISA procedure (Technoclone) was used to determine the plasma vitronectin levels. Results: Plasma vitronectin levels in patient with CAD (% 125.87 ± 58.38) were found to be significantly higher than control group (% 89.47 ± 25.3) (p:0.000). In addition, in patients with double vessel disease (% 146.03 ± 71.69) plasma vitronectin levels were significantly higher than no vessel disease (% 87.84 ± 22.30) and control group, triple vessel disease (% 160.81 ± 57.02) significantly higher as compare with no, single vessel disease (% 111.68 ± 45.34) and control group (p < 0.05). There was no correlation between vitronectin and lipid parameters. Conclusion: These findings suggested that vitronectin is a marker of CAD. Elevated levels may indicate its role in the genesis and/or progression of CAD or may be the results of a compensatory mechanism.

Evaluation of Fibronectin, Vitronectin, and Leptin Levels in Coronary Artery Disease: Impacts on Thrombosis and Thrombolysis

In this study, the levels of fibronectin, vitronectin, leptin, tissue plasminogen activator (t-PA), and lipid parameters were investigated in patients with coronary artery disease (CAD) and control group. The average plasma fibronectin levels in CAD patients group were significantly higher compared with the control group (p=0.006). Moreover, in patients with triple-vessel disease, plasma fibronectin levels were found to be significantly higher than those in the control group (p<0.05). Plasma vitronectin levels in patients with CAD were found to be significantly higher than those in the control group (p=0.000). In addition, in patients with double vessel disease plasma vitronectin levels were significantly higher than no vessel disease and control group, triple vessel disease was significantly higher as compared with no vessel disease, single vessel disease, and control group (p<0.05). We could not find any significant differences in t-PA values between CAD patients and control group. On the other hand, the avarage leptin levels in the group of patients were higher than those in the control group but there were no statistically significant differences found between them (p>0.05) because of high SD values. There was strong (+) correlation between fibronectin, vitronectin, and severity of disease [vitronectin/severity of disease, r = 0.5074 (p = 0.000), fibronectin/severity of disease, r = 0.2971 (p = 0.007)]. In conclusion, we can say that fibronectin and vitronectin have become greatly important in pathogenesis of coronary artery disease. High leptin levels may be contribute to platelet aggregation in patients with coronary artery disease. But, elevated serum levels of leptin cannot be useful diagnostic and monitoring markers in patients with coronary artery disease.

Carbohydrate-Deficient Transferrin and Sialidase Levels in Coronary Heart Disease

Transferrin is a N-glycosylated glycoprotein and plays an important role in iron transport from sites of absorption and storage to sites of utilization. The main component of normal serum transferrin contains two biantennary glycans, each consisting of 2 mol of sialic acid (Tetrasialo transferrin). Normal serum also contains small amounts of tri- and disialotransferrin. We have undertaken this study to investigate the levels of serum carbohydrate-deficient transferrin (Desialotransferrin) and sialidase levels in patients with coronary heart disease. In patient group, serum desialotransferrin and sialidase levels were found to be significantly higher than control group (p < 0.01 and p < 0.001, respectively). We conclude that increased activity of sialidase may be responsible for increased desialotransferrin in patients with coronary heart disease. Serum desialotransferrin levels may be useful critaria to diagnosis and pathogenesis of coronary heart disease.

Preliminary Study Showing the Relationship Between Platelet Fibronectin, Sialic Acid, and ADP-induced Aggregation Levels in Coronary Heart Disease:

Several studies indicate that thrombosis plays an important role in the pathogenesis of coronary heart disease (CHD). Fibronectin is a multifunctional protein in plasma, other body fluids, and cell surface and plays an important role in platelet functions, including mediation of cell-cell and cell-surface interactions. Sialic acid is a regular constituent of glycoproteins and gangliozides in the outer cell membrane of mammalian cells. Therefore, the sialic acid content of platelets, which are characterized by their ability to aggregate with each other, can be important in leading to thrombus formation. In this study, platelet fibronectin, sialic acid-, and adenosine diphosphate (ADP)-induced platelet aggregation levels were determined in patients with CHD. Platelet sialic acid concentrations were determined by Warrens method. Platelet aggregation tests with ADP in platelet-rich plasma (PRP) were analyzed by use of an aggregometer. Platelet homogenate fibronectin levels were determined by ELISA. Total protein levels were determined by Lowry method. Our results indicate that, in patients with no vessel disease (patients with no obstructed vessel but suffering from chest pain, like angina pectoris) platelet fibronectin levels were significantly lower than the total of the other patients (patients with 1, 2, or 3 obstructed coronary vessels) (p<0.05). Sialic acid levels in patients with no vessel disease were significantly lower than the total of the patient group (p<0.05). There was significant (+) correlation between platelet aggregation, platelet fibronectin, platelet sialic acid, and severity of disease (p<0.05). Our preliminary findings suggest that, especially platelet fibronectin levels potentially represent a pathogenic factor for CHD.

Factor VII levels in patients undergoing coronary angiography: factor VII and coronary artery disease.

Background Factor VII (F VII) has been widely investigated as a risk factor for coronary atherosclerosis, however there is still debate about its role in the progression of coronary artery disease (CAD). In this study F VII levels were measured in patients with angiographically proven CAD and its relation with disease severity, coronary events and with other risk factors of coronary atherosclerosis were examined. Methods Consecutive patients referred to coronary angiography were divided in three groups: 1. CAD group -those with a significant lesion in one or more coronary arteries (n = 155), 2. High-risk group - patients with normal coronary arteries and with two or more risk factors (n = 54), 3. Controls - patients with normal coronary arteries and with no or one risk factor (n = 90). CAD group was also studied according to the number of vessels involved and to the history of coronary events. Results Mean F VII levels were not different between the three groups of patients. In CAD group, F VII increased parallel to the number of vessels involved (one vessel disease: 85 ± 20%, two vessel disease: 92 ± 23%, three vessel disease: 105 ± 23%). Patients with a history of coronary events had significantly higher F VII levels than those without such a history (96 ± 25% versus 89 ± 22% respectively, P = 0.02). However, logistic regression analysis revealed no significant relation between F VII and either the presence of CAD or coronary events. Conclusions F VII levels increase in patients with previous coronary events, but it is not an independent risk factor for the progression or for the severity of CAD.

Heterogenous glycogen storage disease in one family.

Three brothers, aged 17, 14 and 4 ye presented. Deficiency of glucose-6-phosphatase was associated with deficiency of acid maltase in one and debranching enzyme in the other. Enzyme analyses could not be performed in the youngest sibling.