Alpha-galactosidase A deficiency leads to increased tissue fibrin deposition and thrombosis in mice homozygous for the factor V Leiden mutation.
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 alpha-galactosidase A (GLA) deficiency, is associated with premature vascular events that may be thrombotic in nature.


METHODS
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.
Shen
Yuechun
Y
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
Bodary
Peter F
PF
Vargas
Fernando B
FB
Homeister
Jonathon W
JW
Gordon
David
D
Ostenso
Kristen A
KA
Shayman
James A
JA
Eitzman
Daniel T
DT
D000818:Animals; D000795:Fabry Disease; D005165:Factor V / Q000235:genetics*; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D006720:Homozygote; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D013194:Staining and Labeling; D013927:Thrombosis / Q000209:etiology* / Q000473:pathology; D000519:alpha-Galactosidase / Q000235:genetics
C095381:factor V Leiden; D005165:Factor V; D005337:Fibrin; D000519:alpha-Galactosidase