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Open AccessArticle

Genetic Variants in the Promoter Region of the Macrophage Migration Inhibitory Factor are Associated with the Severity of Hepatitis C Virus-Induced Liver Fibrosis

1
Department of Internal Medicine III, RWTH Aachen University Hospital, 52074 Aachen, Germany
2
Institute of Human Genetics, RWTH Aachen University Hospital, 52074 Aachen, Germany
3
Department of Intensive Care Medicine, RWTH Aachen University Hospital, 52074 Aachen, Germany
4
Chair of Vacular Biology, Institute for Stroke and Dementia Research (ISD), Ludwig-Maximilians-University (LMU), 81377 Munich, Germany
5
Munich Cluster for Systems Neurology (EXC 2145 SyNergy), 81377 Munich, Germany
6
Section of Hepatology, Clinic for Gastroenterology, University Hospital Leipzig, 04103 Leipzig, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(15), 3753; https://doi.org/10.3390/ijms20153753
Received: 26 June 2019 / Revised: 25 July 2019 / Accepted: 28 July 2019 / Published: 31 July 2019
Two polymorphisms in the promoter region of macrophage migration inhibitory factor (MIF)—rs755622 and rs5844572—exhibit prognostic relevance in inflammatory diseases. The aim of this study was to investigate a correlation between these MIF promoter polymorphisms and the severity of hepatitis C virus (HCV)-induced liver fibrosis. Our analysis included two independent patient cohorts with HCV-induced liver fibrosis (504 and 443 patients, respectively). The genotype of the single nucleotide polymorphism (SNP) -173 G/C and the repeat number of the microsatellite polymorphism -794 CATT5–8 were determined in DNA samples and correlated with fibrosis severity. In the first cohort, homozygous carriers of the C allele in the rs755622 had lower fibrosis stages compared to heterozygous carriers or wild types (1.25 vs. 2.0 vs. 2.0; p = 0.03). Additionally, ≥7 microsatellite repeats were associated with lower fibrosis stages (<F2) (p = 0.04). Comparable tendencies were observed in the second independent cohort, where fibrosis was assessed using transient elastography. However, once cirrhosis had been established, the C/C genotype and higher microsatellite repeats correlated with impaired liver function and a higher prevalence of hepatocellular carcinoma. Our study demonstrates that specific MIF polymorphisms are associated with disease severity and complications of HCV-induced fibrosis in a stage- and context-dependent manner. View Full-Text
Keywords: HCV; liver fibrosis; macrophage migration inhibitory factor; promoter polymorphisms; hepatocellular carcinoma; biomarker HCV; liver fibrosis; macrophage migration inhibitory factor; promoter polymorphisms; hepatocellular carcinoma; biomarker
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Wirtz, T.H.; Fischer, P.; Backhaus, C.; Bergmann, I.; Brandt, E.F.; Heinrichs, D.; Koenen, M.T.; Schneider, K.M.; Eggermann, T.; Kurth, I.; Stoppe, C.; Bernhagen, J.; Bruns, T.; Fischer, J.; Berg, T.; Trautwein, C.; Berres, M.-L. Genetic Variants in the Promoter Region of the Macrophage Migration Inhibitory Factor are Associated with the Severity of Hepatitis C Virus-Induced Liver Fibrosis. Int. J. Mol. Sci. 2019, 20, 3753.

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