Effect of glucocorticoids on von Willebrand factor levels and its correlation with von Willebrand factor gene promoter polymorphism

Abstract

von Willebrand factor (vWF) gene promoter polymorphism at nucleotide positions −2659 and −2525 influences corticosteroid-mediated increase in vWF level and possibly hypercoagulability of the blood. This study was undertaken to correlate plasma vWF levels with plasma cortisol and single nucleotide polymorphisms (SNPs) at positions −2659 and −2525 in Cushing syndrome patients in India. Samples from 22 endogenous and 28 exogenous Cushing syndrome patients and 50 normal volunteers were analyzed to determine vWF level and SNPs. vWF level was raised in 40.91% of endogenous and 14.29% of exogenous Cushing syndrome patients. A positive correlation was seen between plasma cortisol and vWF level (P = 0.01) with 1 μg/ml rise of plasma cortisol causing a 2.52 IU/dl increase in vWF level. Allele frequency of SNPs −2659A, −2659G, −2525A and −2525G was 0.78, 0.22, 0.84 and 0.16, respectively, making cosegregation of −2659A and −2525A the most frequent in our population. Haplotype 1 (−2659A, −2525G) was most frequently associated with higher level of vWF. Patients with haplotype 2 (−2659G, −2525A) had normal vWF. vWF promoter polymorphisms influence corticosteroid-mediated increase in vWF especially in patients with haplotype 1.