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Front. Genet. | doi: 10.3389/fgene.2018.00055

Macrophage Migration Inhibitory Factor –173 G/C Polymorphism: A global meta-analysis across the disease spectrum

  • 1Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Mexico
  • 2División de Investigación Básica, Instituto Nacional de Geriatría, Mexico
  • 3Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico
  • 4Departamento de Biología Molecular, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico

Human macrophage migration inhibitory factor (MIF) is a cytokine that plays a role in several metabolic and inflammatory processes. Single nucleotide polymorphism (SNP) -173 G/C (rs755622) on MIF gene has been associated with numerous diseases, such as arthritis and cancer. However, most of the reports concerning the association of MIF with these and other pathologies are inconsistent and remain quite controversial. Therefore, we performed a meta-analysis from 96 case-control studies on -173 G/C MIF SNP and stratified the data according to the subjects geographic localization or the disease pathophysiology, in order to determine a more meaningful significance to this SNP. The polymorphism was strongly associated with an increased risk in autoimmune-inflammatory, infectious and age-related diseases on the dominant (OR: 0.74 [0.58-0.93], P-val<0.01; OR: 0.81 [0.74-0.89], P-val<0.0001; and OR: 0.81 [0.76-0.87], P-val<0.0001, respectively) and the recessive models (OR: 0.74 [0.57-.095], P-val<0.01; OR: 0.66 [0.48-0.92], P-val<0.0154; and OR: 0.70 [0.60-0.82], P-val<0.0001, respectively). Also, significant association was found in the geographic localization setting for Asia, Europe and Latin America subdivisions in the dominant (OR: 0.76 [0.69-0.84], Pval: <0.0001; OR: 0.77 [0.72-0.83], Pval: <0.0001; OR: 0.61 [0.44-0.83], Pval: 0.0017, respectively) and overdominant models (OR: 0.85 [0.77-0.94], Pval: <0.0001; OR: 0.80 [0.75-0.86], Pval: <0.0001; OR: 0.73 [0.63-0.85], Pval: 0.0017, respectively). Afterwards, we implemented a network meta-analysis to compare the association of the polymorphism for two different subdivisions. We found a stronger association for autoimmune than for age-related or autoimmune-inflammatory diseases, and stronger association for infectious than for autoimmune-inflammatory diseases. We report for the first time a meta-analysis of rs755622 polymorphism with a variety of stratified diseases and populations. The study reveals a strong association of the polymorphism with autoimmune and infectious diseases. These results may help direct future research on MIF -173 G/C in diseases in which the relation is clearer and thus assist the search for more plausible applications.

Keywords: Meta-analysis, MIF, Inflammation, Autoimmune, age-related

Received: 01 Nov 2017; Accepted: 06 Feb 2018.

Edited by:

Dana C. Crawford, Case Western Reserve University, United States

Reviewed by:

Phillip E. Melton, University of Western Australia, Australia
Mohammed A. Al Balwi, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia  

Copyright: © 2018 Illescas Pomposo, Gomez-Verjan, García-Velázquez, Govezensky and Rodriguez-Sosa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Miriam Rodriguez-Sosa, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México, Unidad de Biomedicina, Avenida de Los Barrios 1, Los Reyes Ixtacala, Tlalnepantla México, 54090, Estado de México, Mexico, rodriguezm@unam.mx