Chapter 7 Genetic Aspects of the Antiphospholipid Syndrome: Association with Clinical Manifestations

Although the antiphospholipid syndrome (APS) is considered to be an autoantibody-mediated disease, there is now evidence that antiphospholipid antibodies (aPL) are necessary but not sufficient to trigger the clinical manifestations that characterize the APS. Several genetic determinants may play a key role in inducing the thrombotic events in the presence of aPL. Thromboses in APS are supposed to be a result of the interaction of aPL with a predetermined genetic profile. Several prothombotic genetic characteristics have been studied in APS, including the major thrombophilia determinants (antithrombin and protein C and S deficiencies, factor V Leiden, and G20210A prothrombin mutation) and numerous polymorphisms affecting proteins directly related to aPL (β2 glycoprotein I, and platelet Fcγ receptor IIA), to hemostasis components (platelet glycoproteins, type 1 plasminogen activator inhibitor, tissue factor pathway inhibitor, and factor XIII), and to metabolic, immune, or inflammatory pathways (methylenetetrahydrofolate reductase, P-selectin, P-selectin glycoprotein ligand 1, CD40 ligand, tumor necrosis factor-alpha, angiotensin-converting enzyme, mannose-binding lectin polymorphisms, and toll-like receptor 4 polymorphisms). In this chapter, studies on these genetic determinants associated with clinical manifestations in the APS are reviewed and discussed. © 2009 Elsevier B.V. All rights reserved.