The alpha-2-antiplasmin Arg407Lys polymorphism is associated with Abdominal Aortic Aneurysm

Introduction: Abdominal Aortic Aneurysm(AAA) involves dilatation of the abdominal aorta, with a natural history of expansion and eventual rupture. We have previously shown that AAA patients form denser clots with smaller pores, which are more resistant to fibrinolysis. The aim of this study was to use functional polymorphisms of the fibrinolytic system to identify how changes to proteins involved in fibrinolysis may play a role in the development of AAA. Methods: Caucasian subjects >= 55 years (602 AAA patients and 490 matched controls) were genotyped for four polymorphisms (alpha-2-antiplasmin alpha 2AP Arg6Trp and Arg407Lys, Thrombin-activatable fibrinolysis inhibitor TAFI Thr325Ile and tissue plasminogen activator tPA 7351C -> T). DNA was extracted from blood, and genotype identified using real time PCR. Fibrin clot structure was analysed by permeation and turbidity in a subset of patients and controls. Results: Genotypes across the study population were in Hardy-Weinberg Equilibrium. The two alpha 2AP polymorphisms, Arg6Trp and Arg407Lys were in linkage disequilibrium (P < 0.0001), and possession of a 407Lys allele negatively associated with AAA (odds ratio 0.833, CI95 0.7-0.991, P = 0.040). The TAFI Thr325Ile and the tPA 7351C -> T polymorphisms were not associated with AAA. The alpha 2AP 407Lys allele was not associated with in-vitro fibrinolysis times in plasma from patients with AAA. Conclusion: Possession of the alpha 2AP 407Lys allele was negatively associated with AAA, and thus changes in alpha 2AP may affect aneurysm growth and development. These data indicate that the regulation of plasmin activity (through binding to alpha 2AP), rather than plasmin generation (TAFI, tPA), may play a role in AAA. (C) 2014 Elsevier Ltd. All rights reserved.