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

• Published in: Molecular genetics & genomic medicine 2020-01, Vol.8 (1), p.e1037-n/a
• Main Authors: Santoscoy‐Ascencio, Guillermo, Baños‐Hernández, Christian Johana, Navarro‐Zarza, José Eduardo, Hernández‐Bello, Jorge, Bucala, Richard, López‐Quintero, Andres, Valdés‐Alvarado, Emmanuel, Parra‐Rojas, Isela, Illades‐Aguiar, Berenice, Muñoz‐Valle, José Francisco
• Format: Article
• Language: English
• Subjects: Adult; Aged; Arthritis; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - pathology; Control methods; Cytokines; DAS28; Disease; Disease control; Enzymes; Ethics; Family medical history; Female; Fibroblasts; Gene expression; genetic susceptibility; Genotypes; Genotyping; Haplotypes; Humans; Inflammation; Intramolecular Oxidoreductases - blood; Intramolecular Oxidoreductases - genetics; Intramolecular Oxidoreductases - metabolism; Leukocyte migration; Life sciences; Macrophage migration inhibitory factor; Macrophage Migration-Inhibitory Factors - blood; Macrophage Migration-Inhibitory Factors - genetics; Macrophage Migration-Inhibitory Factors - metabolism; Macrophages; Male; Matrix metalloproteinase; Matrix metalloproteinases; Metalloproteinase; Mexico; Middle Aged; MIF; Original; Polymorphism; Polymorphism, Single Nucleotide; polymorphisms; Population; Promoter Regions, Genetic; Rheumatoid arthritis; Rheumatology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Serum levels; Statistical analysis
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.1037

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. MIF −794CATT5‐8 and −173G > C polymorphisms are not associated with RA susceptibility risk in a southern Mexican population. The 7,7 (−794CATT5‐8) and GC (−173G > C) genotypes are associated with high‐ and low disease activity, respectively. Higher MIF serum levels are associated with moderate disease activity in RA patients.