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Wirtz, Theresa Hildegard; Fischer, Petra; Backhaus, Christina; Bergmann, Irina; Brandt, Elisa Fabiana; Heinrichs, Daniel; Koenen, Maria Teresa; Schneider, Kai Markus; Eggermann, Thomas; Kurth, Ingo; Stoppe, Christian; Bernhagen, Jürgen; Bruns, Tony; Fischer, Janett; Berg, Thomas; Trautwein, Christian; Berres, Marie-Luise (2019): Genetic Variants in the Promoter Region of the Macrophage Migration Inhibitory Factor are Associated with the Severity of Hepatitis C Virus-Induced Liver Fibrosis. In: International Journal of Molecular Sciences, Vol. 20, No. 15, 3753
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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 CATT(5-8) 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.