ABO blood group genotypes, plasma von Willebrand factor levels and loading of von Willebrand factor with A and B antigens.
ABO blood group is a genetic determinant of von Willebrand factor (VWF) levels. We investigated the effect of ABO genotypes on VWF and factor VIII (FVIII) levels and on the degree to which VWF is loaded with A- and B-antigens, expressed as normalized ratios, nA-ratio and nB-ratio, respectively, in the Leiden Thrombophilia Study, a large case-control study on venous thrombosis. We found that the ABO locus had an allele-specific, dosage dependent effect on VWF and FVIII levels and on the loading of VWF with A-antigen and B-antigen. The highest mean nA- and nB-ratios were found in A(1)A(1) and BB genotypes, respectively. Four A(1)O carriers had four 43-bp repeats in the minisatellite region of the ABO gene in stead of the expected one repeat. All had a reduced nA-ratio compared to A(1)O carriers with one repeat in their A(1) allele. The amount of A- and B-antigens expressed onVWF (nA-ratio and nB-ratio) explained about 18% (R(2)) of the variation in VWF levels.
Morelli
Vania M
VM
Hemostasis and Thrombosis Research Center, Dept of Hematology, Leiden University Medical Center, C2-R, Leiden, The Netherlands.
de Visser
Marieke C H
MC
van Tilburg
Nico H
NH
Vos
Hans L
HL
Eikenboom
Jeroen C J
JC
Rosendaal
Frits R
FR
Bertina
Rogier M
RM
D000017:ABO Blood-Group System / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001789:Blood Group Antigens / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005169:Factor VIII / Q000378:metabolism*; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D011159:Population Surveillance; D011485:Protein Binding; D020246:Venous Thrombosis / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism*
D000017:ABO Blood-Group System; D001789:Blood Group Antigens; D014841:von Willebrand Factor; D005169:Factor VIII