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; Maria Grazia Cattini; Elena Pontara; Francesca Sartorello; Lisa Gallinaro; Alberto Marotti; Carla Scaroni; Antonio Pagnan; Alessandra Casonato

doi:10.1160/TH08-08-0501

Thrombosis and Haemostasis, Table of Contents

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

Authors

Viviana Daidone

¹Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Padua, Italy
Maria Grazia Cattini

¹Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Padua, Italy
Elena Pontara

¹Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Padua, Italy
Francesca Sartorello

¹Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Padua, Italy
Lisa Gallinaro

¹Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Padua, Italy
Alberto Marotti

²Padua Blood Bank, Padua, Italy
Carla Scaroni

³Endocrinology, University of Padua Medical School, Padua, Italy
Antonio Pagnan

¹Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Padua, Italy
Alessandra Casonato

¹Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Padua, Italy

Abstract

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

Full Text

References

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