High levels of coagulation factor XI (FXI) have been associated with venous thrombosis, cerebrovascular events and myocardial infarction. Genes involved in the biosynthesis, processing and survival in plasma of coagulation factors are candidate to play pleiotropic effects on circulating levels. It has been inferred from RAP inhibition that the LDL receptor-related protein (LRP) participates in the internalization of the FXIa-protease nexin 1 complex by human fibroblasts. The ABO blood group genotypes, predicting variation in post-translational modifications, are well known determinants of FVIII and vWF plasma levels but their influence on FXI levels has not been report. We investigated whether LRP genotypes might contribute to FXI level variations and interact with ABO genotypes. The LRP genotypes were found to influence FXI levels only in non-O subjects, suggesting that ABO-presenting antigens could produce differential LRP interactions either directly or mediated by other proteins. These hypothesis-generating findings would stimulate further investigation of LRP binding properties in relation to ligand post-translational modifications. Although our results await confirmation in other populations, they provide evidence for the first genetic components with a modest influence on FXI variance in plasma, and highlight a very frequent genetic combination (non-O/LRP –25CC) characterized by the highest mean FXI levels.
Influence of low-density lipoprotein (LDL) receptor-related protein and ABO blood group genotypes on factor XI levels.
MARCHETTI, Giovanna;LUNGHI, Barbara;MAZZONI, Gianni;BERNARDI, Francesco
2008
Abstract
High levels of coagulation factor XI (FXI) have been associated with venous thrombosis, cerebrovascular events and myocardial infarction. Genes involved in the biosynthesis, processing and survival in plasma of coagulation factors are candidate to play pleiotropic effects on circulating levels. It has been inferred from RAP inhibition that the LDL receptor-related protein (LRP) participates in the internalization of the FXIa-protease nexin 1 complex by human fibroblasts. The ABO blood group genotypes, predicting variation in post-translational modifications, are well known determinants of FVIII and vWF plasma levels but their influence on FXI levels has not been report. We investigated whether LRP genotypes might contribute to FXI level variations and interact with ABO genotypes. The LRP genotypes were found to influence FXI levels only in non-O subjects, suggesting that ABO-presenting antigens could produce differential LRP interactions either directly or mediated by other proteins. These hypothesis-generating findings would stimulate further investigation of LRP binding properties in relation to ligand post-translational modifications. Although our results await confirmation in other populations, they provide evidence for the first genetic components with a modest influence on FXI variance in plasma, and highlight a very frequent genetic combination (non-O/LRP –25CC) characterized by the highest mean FXI levels.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
