ASSOCIATION OF FIBRINOLYTIC PARAMETERS AND PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1) GENE 4G/5G PROMOTER POLYMORPHISM WITH SLE

Background: Systemic lupus erythematosus (SLE) is a systemic inflammatory disease that mainly affects women. Although treatment has improved during recent decades, patients with SLE appear to have increased morbidity and mortality from cardiovascular disease. Mutations in the Plasminogen activator inhibitor-1 gene, along with altered plasminogen activator inhibitor-1(PAI-1) levels and tissue plasminogen activator (tPA) have been shown to be independent predictors for atherothrombotic events.Objectives: In this study we aimed to evaluate the plasma levels of PAI-1 and tPA in SLE patients. Also we investigated the association of 4G/5G polymorphism in SLE patients.Methods: Plasma PAI-I ve tPA levels were measured in the plasma of 85 SLE patients (F/M: 82/3, mean age 37±10 years), 19 patients with Takayasu Arteritis (TA) (F/M:18/1, mean age 34±8 years) as control group and 80 healthy controls(HC)(F/M:78/2, mean age 35±10 years) using ELISA. We examined traditional risk factors, novel markers of cardiovascular disease (C-reactive protein, homocystein, fibrinogen) in SLE patients. Common carotid intima-media thickness measurement (IMT) and plaque number determined by B-mode ultrasound as a surrogate measure of atherosclerosis in SLE patients. PAI-1 4G/5G polymorphism was determined by single specific primer-PCR.method.Results: We observed significantly high plasma tPA levels in both SLE (p=0.004) and Takayasu arteritis(p=0.004) patients compared to healthy controls (SLE: 10.7.2±9.4 ng/ml, TA: 11.3±5 ng/ml and HC: 7.2±5.4 ng/ml). Plasma PAI-1 level was significantly higher in SLE patients compared to TA patients (p=0.02) and healthy control (p=0.03) (SLE: 17.1±16 ng/ml, TA: 9.3±10 ng/ml and HC: 12.1±12.2 ng/ml). We observed no significant correlation between plasma PAI -1 levels and PAI 4G/5G genotypes.Significant correlation was observed between age of diagnosis and plaque number of carotid arteries in SLE patients (p:0.001, RR=0.58). No significant difference between PAI-I and tPA plasma levels with clinical manifestations and angiographic findings of TA patients was observed.Conclusion: Inflammation is a prominent feature of atherosclerotic lesions, and systemic inflammation is associated with enhanced risk of atherosclerosis. This study demonstrates that both tPA and PAI-I levels in plasma among SLE patients were significantly higher compared to healthy controls. It may be concluded that increased fibrinolytic activity may be an additional risk factor in development of atherosclerosis in SLE patients.Citation: Ann Rheum Dis, volume 67, supplement II, year 2008, page 213Session: SLE, Sjögren's and APS – Clinical aspects and treatment