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. 2020 Jan;8(1):e1037.
doi: 10.1002/mgg3.1037. Epub 2019 Nov 7.

Macrophage migration inhibitory factor promoter polymorphisms are associated with disease activity in rheumatoid arthritis patients from Southern Mexico

Guillermo Santoscoy-Ascencio  1   2 , Christian Johana Baños-Hernández  1   3 , José Eduardo Navarro-Zarza  4 , Jorge Hernández-Bello  1   5 , Richard Bucala  6 , Andres López-Quintero  1   5 , Emmanuel Valdés-Alvarado  1 , Isela Parra-Rojas  3 , Berenice Illades-Aguiar  3 , José Francisco Muñoz-Valle  1   5
Affiliations

Macrophage migration inhibitory factor promoter polymorphisms are associated with disease activity in rheumatoid arthritis patients from Southern Mexico

Guillermo Santoscoy-Ascencio et al. Mol Genet Genomic Med. 2020 Jan.

Abstract

Background: Macrophage migration inhibitory factor (MIF) is a cytokine capable of stimulating inflammatory cytokine and matrix metalloproteinase production from macrophages and synovial fibroblasts, which leads to persistent inflammation and bone degradation, two of the major pathological processes in rheumatoid arthritis (RA). The aim of this study was to evaluate the association of MIF promoter polymorphisms (-794CATT5-8 rs5844572 and -173G > C, rs755622), circulating MIF levels, and mRNA expression with RA susceptibility and disease activity.

Methods: A case-control study was conducted in 200 RA patients and 200 control subjects (CS) from Southern Mexico. Genotyping was performed by conventional PCR and PCR-RFLP methods. MIF mRNA expression was quantified by real-time PCR and MIF serum levels were determined by an ELISA kit.

Results: The 7,7 (-794CATT5-8 ) and -173CC (-173G > C) genotypes were associated with higher disease activity in RA patients. MIF serum levels were increased, and MIF mRNA expression was reduced in RA patients as compared to CS. In addition, RA patients with moderate disease activity had higher MIF levels than those with low disease activity. The -794CATT5-8 and -173G > C MIF polymorphisms were not associated with RA susceptibility.

Conclusion: These results suggest an important role of MIF polymorphisms and MIF serum levels with disease activity in RA.

Keywords: DAS28; MIF; genetic susceptibility; polymorphisms; rheumatoid arthritis.

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Conflict of interest statement

No conflict of interest was declared by the authors.

Figures

Figure 1
Figure 1
Disease activity (DAS28) according to the genotype distribution of MIF polymorphisms in RA. (a) Kruskal–Wallis test showed a significant difference in the DAS28 score according to MIF −794CATT5‐8 genotypes (p = .03); meanwhile, Dunn's multiple comparison test showed differences between the 7,7 and 5,7 genotypes (p = .04) and between 7,7 versus 6,7 genotypes (p = .02). (b) DAS28 score according to MIF −173G > C genotypes. (c) Haplotypes were inferred from homozygous subjects to MIF −794CATT5‐8 and −173G > C polymorphisms. Comparison among groups was performed using Mann–Whitney U test (b, c)
Figure 2
Figure 2
MIF serum levels and MIF mRNA expression. (a) Comparison of MIF serum levels between RA patients and CS. (b) MIF serum levels according to the disease activity score (DAS28) in RA patients. (c) MIF mRNA expression in RA and CS. Statistical analysis was performed using Mann–Whitney U test (a, c) and Dunn's multiple comparison test (b)
Figure 3
Figure 3
Effect of glucocorticoid treatment on MIF serum levels and MIF mRNA expression. (a) Comparison of MIF serum levels between RA patients with or without glucocorticoid treatment. (b) MIF mRNA expression between RA patients with and without glucocorticoid treatment. The medians were compared using the Mann–Whitney U test
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References

    1. Aletaha, D. , Neogi, T. , Silman, A. J. , Funovits, J. , Felson, D. T. , Bingham, C. O. , … Hawker, G. (2010). 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis & Rheumatism, 62(9), 2569–2581. 10.1002/art.27584 - DOI - PubMed
    1. Alourfi, Z. , Donn, R. P. , Stevens, A. , Berry, A. , McMaster, A. , & Ray, D. W. (2005). Glucocorticoids suppress macrophage migration inhibitory factor (MIF) expression in a cell‐type‐specific manner. Journal of Molecular Endocrinology, 34(2), 583–595. 10.1677/jme.1.01647 - DOI - PubMed
    1. Bae, S.‐C. , & Lee, Y. H. (2018). Associations between circulating macrophage migration inhibitory factor (MIF) levels and rheumatoid arthritis, and between MIF gene polymorphisms and disease susceptibility: A meta‐analysis. Postgraduate Medical Journal, 94(1108), 109–115. 10.1136/postgradmedj-2017-134934 - DOI - PubMed
    1. Barton, A. , Lamb, R. , Symmons, D. , Silman, A. , Thomson, W. , Worthington, J. , & Donn, R. (2003). Macrophage migration inhibitory factor (MIF) gene polymorphism is associated with susceptibility to but not severity of inflammatory polyarthritis. Genes and Immunity, 4(7), 487–491. 10.1038/sj.gene.6364014 - DOI - PubMed
    1. Baugh, J. A. , Chitnis, S. , Donnelly, S. C. , Monteiro, J. , Lin, X. , Plant, B. J. , … Bucala, R. (2002). A functional promoter polymorphism in the macrophage migration inhibitory factor (MIF) gene associated with disease severity in rheumatoid arthritis. Genes and Immunity, 3(3), 170–176. 10.1038/sj.gene.6363867 - DOI - PubMed

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