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Abstract
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 < 0.01; OR: 0.81 [0.74–0.89], P < 0.0001; and OR: 0.81 [0.76–0.87], P < 0.0001, respectively) and the recessive models (OR: 0.74 [0.57–0.095], P < 0.01; OR: 0.66 [0.48–0.92], P < 0.0154; and OR: 0.70 [0.60–0.82], P < 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], P < 0.0001; OR: 0.77 [0.72–0.83], P < 0.0001; OR: 0.61 [0.44–0.83], P-value: 0.0017, respectively) and overdominant models (OR: 0.85 [0.77–0.94], P < 0.0001; OR: 0.80 [0.75–0.86], P < 0.0001; OR: 0.73 [0.63–0.85], P-value: 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.
Highlights
Human macrophage migration inhibitory factor (MIF) is a cytokine involved in several metabolic and inflammatory processes, that have been widely studied in recent years
Hardy-Weinberg Equilibrium (HWE) analysis was individually conducted for all cohorts, showing 15 cohort control groups out of HWE, which were not included in further analyses
In the present meta-analysis, 96 control-case studies comprising 100 different cohorts evaluating the relationship of the MIF -173 G/C polymorphism with a variety of diseases were included
Summary
Human macrophage migration inhibitory factor (MIF) is a cytokine involved in several metabolic and inflammatory processes, that have been widely studied in recent years. MIF is a versatile protein that acts as a potent upstream regulator of the immune system. This 12.5-kDa protein plays an important role as a cytokine, chemokine, and even as an enzyme. MIF has proinflammatory activities through the induction of the expression of other inflammatory cytokines and countering the effects of glucocorticoids (Calandra and Bucala, 1997). As a chemokine, it induces chemotaxis and arrests T and B lymphocytes, neutrophils and macrophages (Tillmann et al, 2013; Alampour-Rajabi et al, 2015). MIF exhibits tautomerase and redox activities, which may be associated with the cytokine and chemokine functions of this protein (Nguyen et al, 2003a; Zhang et al, 2016)
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