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 Jul 31;20(15):3753. doi: 10.3390/ijms20153753.


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.

Keywords: HCV; biomarker; hepatocellular carcinoma; liver fibrosis; macrophage migration inhibitory factor; promoter polymorphisms.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Carcinoma, Hepatocellular / diagnostic imaging
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology
  • Cohort Studies
  • Elasticity Imaging Techniques
  • Female
  • Gene Expression
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Hepacivirus / pathogenicity
  • Hepacivirus / physiology
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / diagnostic imaging
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / virology
  • Heterozygote
  • Homozygote
  • Humans
  • Intramolecular Oxidoreductases / genetics*
  • Liver / metabolism
  • Liver / pathology
  • Liver / virology
  • Liver Cirrhosis / diagnostic imaging
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / virology
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / etiology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / virology
  • Macrophage Migration-Inhibitory Factors / genetics*
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Severity of Illness Index


  • Macrophage Migration-Inhibitory Factors
  • Intramolecular Oxidoreductases
  • MIF protein, human