Association of Macrophage Migration Inhibitory Factor-794 CATT Microsatellite Polymorphism With Tuberculosis Risk: A Systematic Review and Meta-Analysis.

BACKGROUND: Tuberculosis (TB) remains a major infectious cause of morbidity and mortality worldwide and is influenced by both environmental exposures and host genetic factors. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, plays an important role in immune and inflammatory responses. The MIF-794 CATT microsatellite polymorphism (rs5844572) in the promoter region may affect gene transcription and thereby influence susceptibility to TB. This systematic review and meta-analysis are aimed at evaluating the association between the MIF-794 CATT polymorphism and TB risk across different populations.

METHODS: A comprehensive literature search was performed in PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar up to the latest available date. Case-control studies evaluating the association between the MIF-794 CATT polymorphism and TB susceptibility were included in accordance with PRISMA guidelines. Data from seven high-quality studies (Newcastle-Ottawa Scale score ≥ 8), comprising 1063 TB cases and 957 controls, were pooled. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated under allelic, dominant, and recessive genetic models using fixed- or random-effects models according to heterogeneity.

RESULTS: The pooled analysis suggested a possible association between longer CATT repeat alleles (CATTor CATT) and increased TB susceptibility compared with shorter repeats (CATTor CATT), although the effect size was modest and not fully consistent across all populations. A stronger trend was observed in some East Asian cohorts, whereas African and Latin American studies showed variable results. All included studies were of high methodological quality, and control groups were reported to be in Hardy-Weinberg equilibrium (HWE). Visual assessment of funnel plots did not indicate marked publication bias, although the small number of studies limits definitive interpretation.

CONCLUSIONS: The available evidence suggests that the MIF-794 CATT polymorphism may contribute to TB susceptibility, but the association remains modest, heterogeneous, and inconclusive overall. This variant should be regarded as a possible component of a broader immunogenetic framework rather than an established standalone biomarker. Further large-scale, multicentric, and functionally integrated studies are needed to clarify its role in TB risk.