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

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...

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Published inThrombosis and haemostasis Vol. 101; no. 2; p. 298
Main Authors Daidone, Viviana, Cattini, Maria Grazia, Pontara, Elena, Sartorello, Francesca, Gallinaro, Lisa, Marotti, Alberto, Scaroni, Carla, Pagnan, Antonio, Casonato, Alessandra
Format Journal Article
LanguageEnglish
Published Germany 01.02.2009
Subjects
ABO Blood-Group System
Adult
Age Factors
Female
Gene Frequency
Haplotypes
Humans
Italy
Linkage Disequilibrium
Male
Microsatellite Repeats
Middle Aged
Phenotype
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Reference Values
von Willebrand Factor - genetics
von Willebrand Factor - metabolism
Italy
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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.
ISSN:0340-6245
DOI:10.1160/TH08-08-0501