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Thromb Haemost 2009; 101(02): 298-304
DOI: 10.1160/TH08-08-0501
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Microsatellite (GT)n repeats and SNPs in the von Willebrand factor gene promoter do not influence circulating von Willebrand factor levels under normal conditions

Viviana Daidone
1   Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Padua, Italy
,
Maria Grazia Cattini
1   Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Padua, Italy
,
Elena Pontara
1   Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Padua, Italy
,
Francesca Sartorello
1   Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Padua, Italy
,
Lisa Gallinaro
1   Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Padua, Italy
,
Alberto Marotti
2   Padua Blood Bank, Padua, Italy
,
Carla Scaroni
3   Endocrinology, University of Padua Medical School, Padua, Italy
,
Antonio Pagnan
1   Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Padua, Italy
,
Alessandra Casonato
1   Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Padua, Italy
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Publikationsverlauf

Received: 04. August 2008

Accepted after major revision: 29. Januar 2008

Publikationsdatum:
23. November 2017 (online)

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Summary

Von Willebrand factor (VWF) levels vary considerably in normal individuals, influenced by inherited and acquired modulators. ABO blood group is the major inherited determinant of VWF levels, but a role has also been attributed to the VWF gene promoter, haplotype 1 (-3268G/-2709C/-2661A/-2527G) being associated with higher VWF levels than haplotype 2 (-3268C/-2709T/-2661G/-2527A), and the polymorphic locus (GT)n modulating the shear stress-induced activation of the VWF promoter. We characterized the (GT)n of the VWF promoter in 394 healthy individuals and assessed whether its variable length influenced VWF levels in normal conditions. (GT)n proved highly polymorphic, with alleles from 15 to 24 repeats long. (GT)21 and (GT)19 were the most common variants (37.4% and 34.4%, respectively). Short GT repeats (15–19) segregated mainly with haplotype 1, long GT repeats (20–24) with haplotype 2 (p<0.0001). The number of GT repeats did not correlate with VWF levels, nor did such levels correlate with haplotypes 1 and 2, considered alone or in association with the (GT)n locus. We conclude that (GT)n and -3268/-2709/-2661/-2527 loci are in strong linkage disequilibrium. This polymorphic region of the VWF promoter does not affect VWF levels under normal conditions, though it might represent an environmentally activable VWF regulation site.

Keywords

von Willebrand factor - (GT)n locus - VWF promoter SNPs - linkage disequilibrium - VWF level variability
 

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