Microsatellite (GT)_n is part of the von Willebrand factor (VWF) promoter region that influences the glucocorticoid-induced increase in VWF in Cushing's syndrome

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• 作者：Viviana Daidone ; Elena Pontara ; Chiara Romualdi ; Maria G. Cattini ; Carla Scaroni ; Nora Albiger ; Antonio Pagnan ; Aless ; ra Casonato
• 关键词：von Willebrand factor ; VWF promoter GT-repeat ; VWF promoter SNPs ; Cushing's syndrome ; hypercoagulable state in CS
• 刊名：Thrombosis Research
• 出版年：2010
• 出版时间：June 2010
• 年：2010
• 卷：125
• 期：6
• 页码：e275-e280
• 全文大小：342 K

文摘

Introduction

The cortisol-induced increase in von Willebrand factor (VWF) in Cushing's syndrome (CS) seems to depend on single nucleotide polymorphisms (SNPs) of the VWF promoter, haplotype 1 (-3268G/-2709C/-2661A/-2527G) being the susceptible pattern.

Materials and Methods

This study focused on a new variable region of the VWF promoter, the -2144(GT)_n locus, to establish whether different GT-repeat lengths are also involved in modulating the cortisol-induced increase in VWF. Sixty-nine CS patients were investigated, divided into groups A (high VWF) and B (normal VWF).

Results

Analysing the (GT)_n locus revealed a similar allele distribution in CS patients and normal subjects, (GT)_n variants ranging from 15 to 24 repeats and (GT)₁₉ and (GT)₂₁ being the two most represented. However, when groups A and B were analysed separately, a different allele distribution was observed: short GT-repeats (15-19, GT_S) were more frequent in group A, long GT-repeats (20-24, GT_L) in group B (p = 0.01). About genotype distributions, (GT)_S/(GT)_S was higher in group A and rare in group B (22.5 % and 3.4 % , respectively), whereas (GT)_L/(GT)_L was higher in group B than in group A (55.2 % , 27.5 % ) (p = 0.021). Odds-ratio analysis revealed a risk of a cortisol-dependent increase in VWF three times higher for alleles (GT)_S than for (GT)_L, and 13-fold for genotype (GT)_S/(GT)_S respect to (GT)_L/(GT)_L.

Conclusions

In conclusion, not only the SNPs haplotypes in the VWF gene promoter, but also the variable-length (GT)_n locus predict the risk of developing high VWF levels under conditions of glucocorticoid excess; the combination of (GT)_S and haplotype 1 represents the susceptible pattern.