[Synergistic effect of deficiency in thrombosis-related genes].
OBJECTIVE
To investigate the interaction of deficiency in thrombosis-related gene in a mouse model.


METHODS
To generate mice carrying mutations in alpha-galactosidase A (Gla) and factor V Leiden (Fvl) and analyze the phenotypes, namely, tissue fibrin deposition and thrombus formation in organs.


RESULTS
Fibrin deposition in organs of mice carrying both mutations in Gla and Fvl was significantly increased compared with that in mice with single mutaton: [Gla(-/0) Fv(Q/Q)+Gla(-/-)Fv(Q/Q)] vs.[Gla(-/0)Fv(+/+)]=(0.28+/-0.03)% vs.(0.07+/-0.007)%, P<0.01; [Gla(-/0)Fv(Q/Q)+Gla(-/-)Fv(Q/Q)] vs.[Gla(+/0)Fv(Q/Q)+Gla(+/+)Fv(Q/Q)]=(0.28+/-0.03)% vs.(0.11+/-0.02)%, P< 0.01. Meanwhile, the number of thrombi on organ sections of mice carrying both mutations in Gla and Fvl was significantly increased compared with the single mutation carrier: [Gla(-/0)Fv(Q/Q)+Gla(-/-)Fv(Q/Q)] vs.[Gla(-/0)Fv(+/+)]=1.9+/-0.7 vs. 0.0+/-0.0, P<0.05; [Gla(-/0)Fv(Q/Q)+Gla(-/-)Fv(Q/Q)] vs. [Gla(+/0)Fv(Q/Q)+Gla(+/+)Fv(Q/Q)]=1.9+/-0.7 vs. 0.3+/-0.1, P<0.05.


CONCLUSIONS
These observations demonstrated that there was synergistic effect in Gla and Fvl deficiency in mice. It suggested that there could be a combination of GLA deficiency and FVL or other thrombosis-related gene defect in patients with genetic severe early-onset thrombosis.
Shen
Yue-chun
YC
Department of Cardiology, First Affiliated Hospital, Guangzhou Medical College, Guangzhou, Guangdong, 510120 PR China.
Luo
Bi-hui
BH
Ou
Bi-ru
BR
Chen
Ai-lan
AL
Wang
Xiao-ming
XM
Li
Jun
J
D000818:Animals; D005165:Factor V / Q000235:genetics*; D005337:Fibrin / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D009154:Mutation; D013927:Thrombosis / Q000235:genetics* / Q000378:metabolism; D000519:alpha-Galactosidase / Q000235:genetics*
C095381:factor V Leiden; D005165:Factor V; D005337:Fibrin; D000519:alpha-Galactosidase