EPCR genindeki olası değişimlerin trombozlu olgularda sEPCR seviyeleri üzerindeki etkisinin araştırılması
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Date
2009
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Biyoteknoloji Enstitüsü
Abstract
The protein C pathway is a physiologically important mechanism for the regulation of the coagulation process. The pathway is triggered when thrombin binds to the endothelial cell surface receptor thrombomodulin. The thrombin-thrombomodulin complex activates protein C. Activated protein C (APC), together with its cofactor protein S, limits the amplification and progression of the coagulation cascade by proteolytic inactivation of factors (F)Va and FVIIIa. This process occurs on the negatively charged surface of activated platelets.Endothelial cell protein C receptor (EPCR) is a type I transmembrane protein that is almost exclusively expressed on the endothelium of large vessels. Binding of protein C (PC) to EPCR stimulates PC activation by increasing the affinity of PC for the thrombin-thrombomodulin complex. EPCR is similar to molecules of the class I major histocompatibility complex, in particular the CD1-subfamily. In addition to the extracellular domains, EPCR has a transmembrane domain and a very short cytoplasmic tail. EPCR gene is located on chromosome 20q11.2. It consists of four exons. A soluble form of this receptor (sEPCR) circulates in plasma and inhibits both PC activation and APC anticoagulant activity.The aim of this study was to investigate the detection of the variations in the EPCR gene which has a role for thrombosis and the effects of this variations on the plasma sEPCR levels. We have 42 thrombotic patients and 29 healthy subject samples that have lower sEPCR levels (sEPCR< 50 ng / ?l) and 74 thrombotic patients and 24 healthy subject samples that have higher sEPCR levels (sEPCR>130 ng / ?l). Following DNA extraction, PCR, SSCP and DNA sequencing analysis of EPCR gene were performed. We detected 3998C>T and 4678 C>G polymorphisms in patients that have known sEPCR levels. The role of 3?UTR at RNA stability is known. Thus, EPCR 3?UTR 4678G>C polymorphism might have important effect on the thrombotic risk.Key Words
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Biyoteknoloji, Biyoloji