|
|
Blood, 15 October 2004, Vol. 104, No. 8, pp. 2359-2367.
Prepublished online as a Blood First Edition Paper on June 29, 2004; DOI 10.1182/blood-2004-01-0349.
 Previous Article | Next Article 
Submitted February 4, 2004
Accepted June 2, 2004
An association of candidate gene haplotypes and bleeding severity in Von Willebrand Disease (VWD) type 1 pedigrees
Thomas J Kunicki*, Augusto B Federici, Daniel R Salomon, James A Koziol, Steven R Head, Tony S Mondala, Jeffrey D Chismar, Luciano Baronciani, Maria Teresa Canciani, and Ian R Peake
Roon Research Center for Arteriosclerosis and Thrombosis, The Scripps Research Institute, La Jolla, CA, USA; Division of Experimental Hemostasis and Thrombosis, The Scripps Research Institute, La Jolla, CA, USA
Department of Internal Medicine and Dermatology, IRCCS Maggiore Hospital and University of Milan, Milan, Italy
Division of Experimental Hemostasis and Thrombosis, The Scripps Research Institute, La Jolla, CA, USA; DNA Array Core Facility, The Scripps Research Institute, La Jolla, CA, USA
Division of Biostatistics of the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA
DNA Array Core Facility, The Scripps Research Institute, La Jolla, CA, USA
Division of Genomic Medicine, Royal Hallamshire Hospital, Sheffield, United Kingdom
* Corresponding author; email: tomk{at}scripps.edu.
Von Willebrand Disease (VWD) type 1 is difficult to diagnose because of bleeding variability and low heritability of Von Willebrand Factor (VWF) levels. We compared a bleeding severity score and bleeding times to candidate gene haplotypes within pedigrees of fourteen index cases, using a covariance components model for multivariate traits (Mendel: QTL Association). These pedigrees included 13 affected and 40 unaffected relatives, as defined by plasma Ristocetin cofactor (VWF:RCo) levels. The bleeding severity score was derived from a detailed history. Donors were genotyped using a primer extension method, and nine candidate genes were selected for analysis. VWF:RCo levels had the strongest influence on bleeding severity score and bleeding time. ITGA2 haplotype 2 (807C) and ITGA2B haplotype 1 (Ile843) were each associated with increased bleeding severity scores (p=0.00009 and p = 0.00496, respectively). GP6 haplotype b (Pro219) was also associated with increased scores (p = 0.02912) after adjustment for donor age. No association was observed with six other candidate genes, GP1BA, ITGB3, VWF, FGB, IL6 or TXA2R. Increased plasma VWF:Ag levels were associated with VWF haplotype 1 (-1793G) (p=0.02314). These results establish that genetic differences in the adhesion receptor subunits  2, IIb and GPVI can influence the phenotype of VWD type1.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. Goodeve, J. Eikenboom, G. Castaman, F. Rodeghiero, A. B. Federici, J. Batlle, D. Meyer, C. Mazurier, J. Goudemand, R. Schneppenheim, et al.
Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD)
Blood,
January 1, 2007;
109(1):
112 - 121.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. P. Riddel Jr. and B. E. Aouizerat
Genetics of von Willebrand disease type 1.
Biol Res Nurs,
October 1, 2006;
8(2):
147 - 156.
[Abstract]
[PDF]
|
|
|
|
|
|
|
D. L. Yee, C. W. Sun, A. L. Bergeron, J.-f. Dong, and P. F. Bray
Aggregometry detects platelet hyperreactivity in healthy individuals
Blood,
October 15, 2005;
106(8):
2723 - 2729.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
