ABO blood group genotypes, plasma von Willebrand factor levels and loading of von Willebrand factor with A and B antigens

 

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Summary

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 A¹ O carriers had four 43-bp repeats in the minisatellite region of theABO 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 A¹ allele. The amount of A – and B- antigens expressed onVWF (nA-ratio and nB-ratio) explained about 18% (R²) of the variation in VWF levels.

• References

• 1 Sadler JE. Biochemistry and genetics of von Willebrand factor. Ann Rev Biochem 1998; 67: 395-424.
  CrossrefPubMedGoogle Scholar
• 2 Mayadas TN, Wagner DD. Von Willebrand factor biosynthesis and processing. Ann NY Acad Sci 1991; 614: 153-166.
  CrossrefPubMedGoogle Scholar
• 3 Wagner DD. The Weibel-Palade body: the storage granule for von Willebrand factor and P-selectin. Thromb Haemost 1993; 70: 105-110.
  Article in Thieme ConnectPubMedGoogle Scholar
• 4 van Mourik JA, Romani de Wit T, Voorberg J. Biogenesis and exocytosis of Weibel-Palade bodies. Histochem Cell Biol 2002; 117: 113-122.
  CrossrefPubMedGoogle Scholar
• 5 Titani K, Kumar S, Takio K. et al. Amino acid sequence of human von Willebrand factor. Biochemistry 1986; 25: 3171-3184.
  CrossrefPubMedGoogle Scholar
• 6 Preston AE, Barr A. The plasma concentration of factor VIII in the normal population. Br J Haematol 1964; 10: 238-245.
  CrossrefPubMedGoogle Scholar
• 7 Ørstavik K, Magnus P, Reisner H. et al. Factor VIII and factor IX in a twin population: evidence for a major effect of ABO locus on factor VIII level. Am J Hum Genet 1985; 37: 89-101.
  PubMedGoogle Scholar
• 8 Gill JC, Endres-Brooks J, Bauer PJ. et al. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987; 69: 1691-1695.
  PubMedGoogle Scholar
• 9 O'Donnell J, Boulton FE, Manning RA. et al. Amount of H antigen expressed on circulating von Willebrand factor is modified by ABO blood group genotype and is a major determinant of plasma von Willebrand factor antigen levels. Arterioscler Thromb Vasc Biol 2002; 22: 335-341.
  CrossrefPubMedGoogle Scholar
• 10 Shima M, Fujimura Y, Nishiyama T. et al. ABO blood group genotype and plasma von Willebrand factor in normal individuals. Vox Sang 1995; 68: 236-240.
  CrossrefPubMedGoogle Scholar
• 11 Souto JC, Almasy L, Muniz-Diaz E. et al. Functional effects of the ABO locus polymorphism on plasma levels of von Willebrand factor, factor VIII, and activated partial thromboplastin time. Arterioscler Thromb Vasc Biol 2000; 20: 2024-2028.
  CrossrefPubMedGoogle Scholar
• 12 Schleef M, Strobel E, Dick A. et al. Relationship between ABO and secretor genotype with plasma levels of factor VIII and von Willebrand factor in thrombosis patients and control individuals. Br J Haematol 2005; 128: 100-107.
  CrossrefPubMedGoogle Scholar
• 13 Kamphuisen PW, Houwing-Duistermaat JJ, van Houwelingen HC. et al. Familial clustering of factor VIII and von Willebrand factor levels. Thromb Haemost 1998; 79: 323-327.
  Article in Thieme ConnectPubMedGoogle Scholar
• 14 Yamamoto F, Clausen H, White T. et al. Molecular genetic basis of the histo-blood group ABO system. Nature 1990; 345: 229-233.
  CrossrefPubMedGoogle Scholar
• 15 Yamamoto F, McNeill PD, Hakomori S. Human histo-blood group A2 transferase coded by A2 allele, one of the A subtypes, is characterized by a single base deletion in the coding sequence, which results in an additional domain at the carboxyl terminal. Biochem Biophys Res Commun 1992; 187: 366-374.
  CrossrefPubMedGoogle Scholar
• 16 Matsui T, Titani K, Mizuochi T. Structures of the asparagines- linked oligosaccharides chains of human von Willebrand factor: occurrence of blood group A, B, and H(O) structures. J Biol Chem 1992; 267: 8723-8731.
  PubMedGoogle Scholar
• 17 O’Donnell JSO, McKinnon TAJ, Crawley JTB. et al. Bombay phenotype is associated with reduced plasma- VWF levels and an increased susceptibility to ADAMTS13 proteolysis. Blood 2005; 106: 1988-1991.
  CrossrefPubMedGoogle Scholar
• 18 Bowen DJ. An influence of ABO blood group on the rate of proteolysis of von Willebrand factor by ADAMTS13. J Thromb Haemost 2003; 1: 33-40.
  CrossrefPubMedGoogle Scholar
• 19 Yu LC, Chang CY, Twu YC. et al. Human histoblood group ABO glycosyltransferase genes: different enhancer structures with different transcriptional activities. Biochem Biophys Res Com 2000; 273: 459-466.
  CrossrefPubMedGoogle Scholar
• 20 Koster T, Rosendaal FR, de Ronde H et al. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet 1993; 342: 1503-1506.
  CrossrefPubMedGoogle Scholar
• 21 Olsson ML, Chester MA. A rapid and simple ABO genotype screening method using a novel B/O2 versus A/O2 discriminating nucleotide substitution at the ABO locus. Vox Sang 1995; 69: 242-247.
  PubMedGoogle Scholar
• 22 Koster T, Blann AD, Briët E. et al. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345: 152-155.
  CrossrefPubMedGoogle Scholar
• 23 Rahat A, Stewart J, Blackwell CC. et al. Semiquantitative determination of H type 1 and type 2 antigens on buccal epithelial cells and in saliva of secretors and non-secretors. Vox Sang 1990; 59: 101-105.
  CrossrefPubMedGoogle Scholar
• 24 Matsui T, Hamako J, Ozeki Y. et al. Comparative study of blood group-recognizing lectins toward ABO blood group antigens on neoglycoproteins, glycoproteins and complex-type oligosaccharides. Biochim Biophys Acta 2001; 1525: 50-57.
  CrossrefPubMedGoogle Scholar
• 25 Morelli VM, de Visser MCH, Vos HL. et al. ABO blood group genotypes and the risk of venous thrombosis: effect of factor V Leiden. J Thromb Haemost 2005; 3: 183-185.
  CrossrefPubMedGoogle Scholar
• 26 Gershan JA, Visentin GP, Curtis BR. et al. Molecular basis for high expression of A antigen on platelets of some normal individuals. Blood 2001; 98: 708a
  PubMedGoogle Scholar
• 27 Souto JC, Almasy L, Soria JM. et al. Genome-wide linkage analysis of von Willebrand factor plasma levels: results from the GAIT project. Thromb Haemost 2003; 89: 468-474.
  Article in Thieme ConnectPubMedGoogle Scholar
• 28 De Visser MCH, Sandkuijl LA, Lensen RP. et al. Linkage analysis of factor VIII and von Willebrand factor loci as quantitative trait loci. J Thromb Haemost 2003; 1: 1771-1776.
  CrossrefPubMedGoogle Scholar
• 29 O'Donnell J, Boulton FE, Manning RA. et al. Genotype at the secretor blood group locus is a determinant of plasma von Willebrand factor level. Br J Haematol 2002; 116: 350-356.
  CrossrefPubMedGoogle Scholar
• 30 Eikenboom JCJ, Castaman G, Kamphuisen PW. et al. The factor VIII/von Willebrand factor ratio discriminates between reduced synthesis and increased clearance of von Willebrand factor. Thromb Haemost 2002; 87: 252-257.
  Article in Thieme ConnectPubMedGoogle Scholar
• 31 Sodetz JM, Pizzo SV, McKee PA. Relationship of sialic acid to function and in vivo survival of human factor VIII/von Willebrand factor protein. J Biol Chem 1977; 52: 5538-5546.
  PubMedGoogle Scholar
• 32 Stoddart Jr JH, Andersen J, Lynch DC. Clearance of normal and type 2A von Willebrand factor in the rat. Blood 1996; 88: 1692-1699.
  PubMedGoogle Scholar
• 33 Mohlke KL, Purkayastha AA, Westrick RJ. et al. Mvwf, a dominant modifier of murine von Willebrand factor, results from altered lineage specific expression of a glycosyltransferase. Cell 1999; 96: 111-120.
  CrossrefPubMedGoogle Scholar
• 34 Biessen EA, Bakkeren HF, Beuting DM. et al. Ligand size is a major determinant of high affinity binding of fucose- and galactose-exposing lipoproteins by the hepatic fucose receptor. Biochem J 1994; 299: 291-296.
  CrossrefPubMedGoogle Scholar
• 35 Ørstavik KH, Kornstad L, Reisner H. et al. Possible effect of Secretor locus on plasma concentration of factor VIII and von Willebrand factor. Blood 1989; 73: 990-993.
  PubMedGoogle Scholar
• 36 Federici AB, Elder JH, De Marco L. et al. Carbohydrate moiety of von Willebrand factor is not necessary for maintaining multimeric structure and ristocetin cofactor activity but protects from proteolytic degradation. J Clin Invest 1984; 74: 2049-2055.
  CrossrefPubMedGoogle Scholar