Quantitative gene expression in Budd-Chiari syndrome: a molecular approach to the pathogenesis of the disease

Valerie Paradis ^1*, Ivan Bieche ², Delphine Dargere ³, Dominique Cazals-Hatem ¹, Ingrid Laurendeau ², Veronique Saada ¹, Jacques Belghiti ¹, Annie Bezeaud ¹, Michel Vidaud ², Pierre Bedossa ¹ and Dominique Charles Valla ¹

¹ Beaujon Hospital, France
² UPRES EA 3618, France
³ CNRS UMR 8149, France

^* To whom correspondence should be addressed. E-mail: vparadis{at}teaser.fr.

Accepted 31 May 2005

Abstract

Background: Budd-Chiari syndrome (BCS) is associated with parenchymal changes leading to major architecture remodeling. In order to gain further insight into the pathogenesis of BCS, we investigated the expression of a set of genes involved in the course of chronic liver diseases.

Methods: Quantitative expression of 35 selected genes involved in extracellular matrix regulation, growth factors and angiogenesis was investigated in 13 cases of BCS and compared to 10 normal livers and 13 cirrhosis by real-time RT-PCR. Differential gene expression was considered as significant for genes showing at least a 2- fold variation with p <0.05.

Results: The expression of 14 genes was significantly increased in BCS versus normal liver, with the highest increase in SCG10. BCS cases were classified according to their evolution and morphological pattern as either acute or chronic in 6 and 7 cases, respectively. Unsupervised hierarchical clustering of acute and chronic BCS cases on the basis of similarity in the gene expression pattern led to distinction between the two groups. Expression of 3 genes was significantly different in acute versus chronic BCS (increase in MMP7 and SCG10, decrease in THBS1 for chronic BCS). Seventeen and 10 genes, mainly involving in extracellular matrix and vascular remodeling, were significantly de-regulated in acute BCS versus normal liver and cirrhosis, respectively.

Conclusion: These results showed that BCS cases display a specific gene expression profile which is different from that of normal liver and cirrhosis; the molecular configuration of BCS can be readily distinguished by its evolution and morphological pattern.

Keywords: SCG10, liver fibrosis, real-time RT-PCR, thrombosis, tissue factor

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