title: Microsatellite (GT)(n) repeats and SNPs in the von Willebrand factor gene promoter do not influence circulating von Willebrand factor levels under normal conditions.
abstract: 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.
authors.affiliation: Department of Medical and Surgical Sciences, via Ospedale Civile 105, Padova, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Daidone
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cattini
authors.forename: Elena
authors.initials: E
authors.lastname: Pontara
authors.forename: Francesca
authors.initials: F
authors.lastname: Sartorello
authors.forename: Lisa
authors.initials: L
authors.lastname: Gallinaro
authors.forename: Alberto
authors.initials: A
authors.lastname: Marotti
authors.forename: Carla
authors.initials: C
authors.lastname: Scaroni
authors.forename: Antonio
authors.initials: A
authors.lastname: Pagnan
authors.forename: Alessandra
authors.initials: A
authors.lastname: Casonato
mesh_terms: D000017:ABO Blood-Group System; D000328:Adult; D000367:Age Factors; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012016:Reference Values; D014841:von Willebrand Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D000017:ABO Blood-Group System; D014841:von Willebrand Factor