Alexis Henry, M.S.

Thesis research performed under the direction of Frank C. Church

ABSTRACT
    Protein C Inhibitor (PCI) is a serine protease inhibitor whose physiological role is not well understood.  This study focuses on six SNPs in PCI that result in an amino acid sequence change: A36V, N45S, K85E, P102A, G198R, and G316R.  All recombinant PCI (rPCI) SNPs were generated, expressed, purified, and compared to recombinant wild type PCI (wt-rPCI).  These SNPs display differences in rPCI's ability to inhibit proteases in a purified in vitro assay.  The rPCI SNPs P102A and G198R were better inhibitors, whereas N45S and G316R were worse inhibitors.  An ex vivo plasma clotting assay was then used to study rPCI SNPs in blood coagulation.  A pronounced anticoagulant effect of PCI in the presence of thrombomodulin was found in clotting plasma.  Compared to wt-rPCI, A36V and K86E were less active, whereas the variant P102A was more active in this system.