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(Stroke. 2006;37:1106.)
© 2006 American Heart Association, Inc.

Research Reports

-Galactosidase A Deficiency Leads to Increased Tissue Fibrin Deposition and Thrombosis in Mice Homozygous for the Factor V Leiden Mutation

Yuechun Shen; Peter F. Bodary; Fernando B. Vargas; Jonathon W. Homeister; David Gordon; Kristen A. Ostenso; James A. Shayman Daniel T. Eitzman

From the Department of Internal Medicine, Division of Cardiovascular Medicine, (Y.S., P.F.B., F.B.V., K.A.O., D.T.E.), Division of Nephrology (J.A.S.), and Department of Pathology (J.W.H., D.G.), University of Michigan Medical Center, Ann Arbor.

Correspondence to Daniel T. Eitzman, MD, 1150 W Medical Center Dr, 7301 MSRB III, Ann Arbor, MI 48109-0644. E-mail deitzman{at}umich.edu

Background— Factor V Leiden (FVL) is a common genetic risk factor for vascular thrombosis in humans. Fabry disease, an X-linked lysosomal storage disorder attributable to -galactosidase A (GLA) deficiency, is associated with premature vascular events that may be thrombotic in nature.

Methods and Results— To examine a potential interaction between FvL and Gla deficiency in vivo, we analyzed tissue fibrin deposition in mice carrying combined mutations in FvL and Gla. Gla deficiency markedly increased tissue fibrin deposition in mice carrying the FvL mutation (0.33±0.03%; n=7) compared with FvL mutation (0.14±0.02%; n=10; P<0.0005).

Conclusions— These observations demonstrate a synergistic interaction between Gla deficiency and FvL toward tissue fibrin deposition in mice. Concomitant mutations in these genes may increase the penetrance of vascular thrombotic events in humans.

Key Words: fibrin • genetics • thrombosis

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