Polymorphisms in von Willebrand factor gene promoter influence the glucocorticoid-induced increase in von Willebrand factor: the lesson learned from Cushing syndrome.
Cushing syndrome (CS) features high-glucocorticoid secretion and an associated hypercoagulable state often involving an increase in von Willebrand factor (VWF). To identify any influence of VWF promoter on glucocorticoid haemostatic effects, four polymorphic positions (-3267, -2708, -2659 and -2525) segregating as haplotypes 1 (GCAG) or 2 (CTGA) were analysed in 50 CS patients with high VWF (group I) and normal VWF (group II) levels, divided by ABO group. Genotype distribution differed significantly between the two groups: in group I, 25.8% had genotype 1/1, 22.6% had 2/2 and 38.7% had 1/2; in group II, 0% had genotype 1/1, 57.9% had 2/2 and 31.6% had 1/2 (P = 0.03). Patients' genotypes also differed from those of controls (P = 0.003 for group I, P = 0.03 for group II). Haplotype 1 was prevalent in group I, haplotype 2 in group II (P = 0.002), both with frequencies differing from controls (P < 0.001 and P = 0.009). By odds ratio analysis, genotype 1/1 carried a 12 times greater risk of high-VWF levels than genotype 2/2, and haplotype 1 carried a five times greater risk than haplotype 2. Our findings suggest that VWF promoter haplotypes influence the corticosteroid-mediated increase in VWF.
Casonato
Alessandra
A
Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Padua, Italy. sandra.casonato@unipd.it
Daidone
Viviana
V
Sartorello
Francesca
F
Albiger
Nora
N
Romualdi
Chiara
C
Mantero
Franco
F
Pagnan
Antonio
A
Scaroni
Carla
C
D000328:Adult; D003480:Cushing Syndrome / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005938:Glucocorticoids / Q000502:physiology*; D006239:Haplotypes; D006487:Hemostasis; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014841:von Willebrand Factor / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
D005938:Glucocorticoids; D014841:von Willebrand Factor; D006854:Hydrocortisone