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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

  • Christian Johana Baños-Hernández
  • José Eduardo Navarro-Zarza
  • Richard Bucala
  • Jorge Hernández-Bello
  • Isela Parra-Rojas
  • María Guadalupe Ramírez-Dueñas
  • Samuel García-Arellano
  • Luis Alexis Hernández-Palma
  • Andrea Carolina Machado-Sulbarán
  • José Francisco Muñoz-ValleEmail author
Original Article

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 

Notes

Funding information

The study was supported by funding from the National Council of Science and Technology (CONACYT) Grant A1-S-8774 (CONACYT Ciencia Básica-Universidad de Guadalajara) assigned to JFMV. Also, CJH-B was a Ph.D. fellow at CONACYT-Mexico (#301502).

Compliance with ethical standards

Informed written consent was obtained from all subjects before enrollment to the study. The investigation was performed according to the ethical guidelines of the 2013 Declaration of Helsinki and was approved by the ethical, investigation, and biosecurity committee of the Hospital General de Chilpancingo “Dr. Raymundo Abarca Alarcón,” Chilpancingo de los Bravo, State of Guerrero, Mexico (CI/317/2016).

Disclosures

None.

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Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  • Christian Johana Baños-Hernández
    • 1
    • 2
  • José Eduardo Navarro-Zarza
    • 3
  • Richard Bucala
    • 4
  • Jorge Hernández-Bello
    • 1
    • 5
  • Isela Parra-Rojas
    • 2
  • María Guadalupe Ramírez-Dueñas
    • 6
  • Samuel García-Arellano
    • 1
    • 5
  • Luis Alexis Hernández-Palma
    • 1
  • Andrea Carolina Machado-Sulbarán
    • 6
  • José Francisco Muñoz-Valle
    • 1
    • 5
    Email author
  1. 1.Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajaraMexico
  2. 2.Doctorado en Ciencias Biomédicas, Facultad de Ciencias Químico-BiológicasUniversidad Autónoma de GuerreroChilpancingo de los BravoMexico
  3. 3.Departamento de Medicina Interna-ReumatologíaHospital General de Chilpancingo “Dr. Raymundo Abarca Alarcón”Chilpancingo de los BravoMexico
  4. 4.Department of Medicine/Section of RheumatologyYale University School of MedicineNew HavenUSA
  5. 5.Instituto Transdisciplinar de Investigación y ServiciosUniversidad de GuadalajaraZapopanMexico
  6. 6.Laboratorio de Inmunología, Centro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajaraMexico

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