Macrophage migration inhibitory factor polymorphisms are a potential susceptibility marker in systemic sclerosis from southern Mexican population: association with MIF mRNA expression and cytokine profile

Clin Rheumatol. 2019 Jun;38(6):1643-1654. doi: 10.1007/s10067-019-04459-8. Epub 2019 Feb 12.

Abstract

Introduction: Systemic sclerosis (SSc) is a complex autoimmune disease, characterized by microvascular lesions, autoimmunity, and fibrosis. It is suggested that MIF participates in the amplification of the proinflammatory process in SSc; moreover, the promoter polymorphisms - 794 CATT5-8 (rs5844572) and - 173G>C (rs755622) in the MIF gene have been associated with an increase in MIF serum levels in several autoimmune diseases. The aim of this study was to analyze the relationship of the - 794 CATT5-8 and - 173G>C MIF polymorphisms with mRNA expression, MIF serum levels, and the Th1/Th2/Th17 cytokine profile in SSc.

Materials and methods: A case-control study was carried out that included 50 patients with SSc and 100 control subjects (CS). Both polymorphisms were genotyped by PCR and PCR-RFLP. MIF levels were measured by ELISA kit. The cytokine profile and the MIF mRNA expression were quantified by BioPlex MagPix system and real-time PCR, respectively.

Results: An association between the - 794 CATT7 and - 173*C MIF alleles and the 7C haplotype with SSc susceptibility was found (p < 0.05). Also, the 7C haplotype was associated with increased MIF mRNA expression (p = 0.03) in SSc. In addition, an increase of IL-1β and IL-6 serum levels in SSc patients was found as well as a positive correlation between MIF serum levels and Th1 and Th17 cytokine profiles.

Conclusion: The MIF 7C haplotype is a susceptibility marker for SSc in the southern Mexican population and is associated with MIF mRNA expression. Moreover, there is a positive correlation between MIF serum levels and Th1 and Th17 inflammatory response in SSc.

Keywords: Cytokine profiles Th1/Th2/Th17; MIF; MIF mRNA expression; Promoter polymorphisms; Systemic sclerosis.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Case-Control Studies
  • Cytokines / blood*
  • Female
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Intramolecular Oxidoreductases / blood
  • Intramolecular Oxidoreductases / genetics*
  • Macrophage Migration-Inhibitory Factors / blood
  • Macrophage Migration-Inhibitory Factors / genetics*
  • Male
  • Mexico
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • Scleroderma, Systemic / blood
  • Scleroderma, Systemic / genetics*
  • Scleroderma, Systemic / immunology
  • Th1 Cells / immunology
  • Th17 Cells / immunology
  • Th2 Cells / immunology

Substances

  • Biomarkers
  • Cytokines
  • Macrophage Migration-Inhibitory Factors
  • RNA, Messenger
  • Intramolecular Oxidoreductases
  • MIF protein, human