New Insight into the Hypercoagulability of Cushing's Syndrome

被引:14
作者
Daidone, Viviana [1 ]
Boscaro, Marco [3 ]
Pontara, Elena [1 ]
Cattini, Maria Grazia [1 ]
Occhi, Gianluca [2 ]
Scaroni, Carla [2 ]
Mantero, Franco [2 ]
Casonato, Alessandra [1 ]
机构
[1] Univ Padua, Sch Med, Dept Cardiol Thorac & Vasc Sci, Chair Internal Med 2, IT-51875 Padua, Italy
[2] Univ Padua, Sch Med, Endocrinol Unit, Dept Med & Surg Sci, IT-51875 Padua, Italy
[3] Polytech Univ Marche, Dept Internal Med, Div Endocrinol, Ancona, Italy
关键词
Cushing's syndrome; Von Willebrand factor; Hypercoagulable state of Cushing's syndrome; Von Willebrand factor promoter single nucleotide polymorphisms; Von Willebrand factor promoter (GT)(n); VON-WILLEBRAND-FACTOR; VWF GENE PROMOTER; DISEASE; STATE; POLYMORPHISMS; ACTIVATION; DIAGNOSIS;
D O I
10.1159/000323765
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Hypercoagulability and a tendency for thromboembolic complications are reported in Cushing's syndrome (CS). The hypercoagulability is due mainly to the cortisol-induced increase in von Willebrand factor (VWF) and factor VIIII. This is not a constant feature of CS, however; it depends on particular single nucleotide polymorphism (SNP) haplotypes in the VWF gene promoter: haplotype 1 (-3268G/-2709C/-2661A/-2527G) confers a greater risk of VWF upregulation by cortisol than haplotype 2 (-3268C/-2709T/-2661G/-2527A). In healthy individuals these SNPs are in linkage disequilibrium with the -2144 (GT)(n) of the VWF promoter: haplotype 1 mainly segregates with short GT repeats (15-19, GTs), haplotype 2 with long repeats (GT >= 20, GT(L)). Methods: We analyzed the (GT)(n) locus, the SNP haplotypes and their association with VWF levels in 80 CS patients in order to precisely define the cortisol-sensitive VWF promoter pattern. CS patients were divided into groups A (increased VWF) and B (normal VWF). Results: Haplotype 1 and (GT)(s) were more frequent in group A patients, and conferred a 9- and 7.5-fold risk of developing high VWF levels, respectively. Haplotype 2 and (GT)(L) were more represented in group B. There was also an unexpected higher prevalence of recombinant SNP haplotypes in CS patients (6.2%) than in normals (0.9%), p = 0.002. Conclusions: Our results indicate that the cortisol-induced increase in VWF may be predicted by VWF promoter polymorphisms, haplotype 1 and (GT)(s) being the sensitive pattern. These represent new markers for defining the prothrombotic risk of CS. The clinical significance, if any, of the increased recombination rate in SNP haplotypes in the VWF promoter warrants further study. Copyright (C) 2011 S. Karger AG, Basel
引用
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页码:121 / 125
页数:5
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