Contribution of low density lipoprotein receptor-related protein genotypes to coagulation factor VIII levels in thrombotic women.
The contribution of low density lipoprotein (LDL) receptor-related protein (LRP) to variance of factor VIII (FVIII) levels in plasma was investigated in thrombotic women through analysis of frequent LRP genotypes. The G allele of the LRP -25C/G polymorphism, predicting increased LRP expression, was associated with 15% and 18% mean reductions of FVIII activity and protein levels, respectively. The combination of -25C/G LRP polymorphism with FVIII D1241E and ABO polymorphisms produced a gradient of FVIII levels, thus supporting the notion that several factors, acting in FVIII biosynthesis, post-translational modification and removal from circulation, have additive effects on the variance of FVIII levels in plasma.
Marchetti
Giovanna
G
Department of Biochemistry and Molecular Biology, University of Ferrara, via Fossato di Mortara n 74, I-44100 Ferrara, Italy.
Lunghi
Barbara
B
Legnani
Cristina
C
Cini
Michela
M
Pinotti
Mirko
M
Mascoli
Francesco
F
Bernard
Francesco
F
D000328:Adult; D005169:Factor VIII / Q000032:analysis* / Q000096:biosynthesis; D005260:Female; D005838:Genotype; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011499:Protein Processing, Post-Translational; D013927:Thrombosis / Q000097:blood*
D026503:Low Density Lipoprotein Receptor-Related Protein-1; D005169:Factor VIII