Muehlbauer, Marcus and Bosserhoff, Anja Katrin and Hartmann, Arndt and Thasler, Wolfgang E. and Weiss, Thomas S. and Herfarth, Hans and Lock, Guntram and Schoelmerich, Juergen and Hellerbrand, Claus (2003) A novel MCP-1 gene polymorphism is associated with hepatic MCP-1 expression and severity of HCV-related liver disease. GASTROENTEROLOGY, 125 (4). pp. 1085-1093. ISSN 0016-5085
Full text not available from this repository.Abstract
Background & Aims: Factors influencing the progression of chronic hepatitis C virus (HCV) infection are poorly understood. Monocyte chemotactic protein-1 (MCP-1) is a potent chemokine, and its hepatic expression is up-regulated during chronic HCV infection mainly in activated hepatic stellate cells (HSC). In this study, we investigated the correlation of the functional -2518 MCP-1 promoter polymorphism with hepatic MCP-1 expression and the disease outcome in patients with HCV. Methods: MCP-1 genotyping was performed in 206 patients and 139 healthy controls. Hepatic MCP-1 messenger RNA (mRNA) expression was quantified by real-time PCR in 58 HCV patients. Cytokine-induced MCP-1 secretion of activated human HSC (n = 13) was determined by enzyme-linked immunosorbent assay (ELISA). Mobility-shift assays were performed using probes corresponding to the MCP-1 promoter sequence (-2511 to -2528) with or without the A to G mutation at -2518. Results: Frequency of MCP-1 genotypes did not differ between HCV patients and controls. However, carriers of the G allele were significantly more frequent in HCV patients with more advanced fibrosis and severe inflammation. In accordance, hepatic MCP-1. mRNA levels were significantly higher in patients with more advanced fibrosis and in patients carrying the G allele. Furthermore, cytokine-induced MCP-1 secretion of HSC isolated from carriers of the G allele was significantly higher, and there was binding activity in nuclear extracts from activated HSC specifically to the G allele, providing a potential mechanism for the differences seen. Conclusions: Inheritance of the -2518 MCP-1 G allele, which appears to affect hepatic MCP-1 expression, may predispose HCV patients to more severe hepatic inflammation and fibrosis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MONOCYTE CHEMOATTRACTANT PROTEIN-1; STELLATE CELLS; C VIRUS; PROMOTER POLYMORPHISM; REGULATORY REGION; PROGRESSION; INFECTION; FIBROSIS; LIPOPOLYSACCHARIDE; SUSCEPTIBILITY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Aug 2021 08:14 |
| Last Modified: | 30 Aug 2021 08:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/38548 |
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