Functional polymorphisms in the gene encoding macrophage migration inhibitory factor (MIF) are associated with active pulmonary tuberculosis.

OBJECTIVE

The role of the cytokine, macrophage migration inhibition factor (MIF) was assessed in tuberculosis. This case-control study investigated whether commonly occurring functional MIF polymorphisms are associated with active tuberculosis as well as with serum levels of MIF, IFN-γ and TNF-α.

METHODS

Two MIF promoter polymorphisms, a functional -794 CATT5-8 microsatellite repeat (rs5844572) and a -173G/C single-nucleotide polymorphism (rs755622), were analysed by PCR and PCR-RFLP, respectively, in 47 patients and 50 healthy subjects. The mRNA level of MIF was performed by real-time PCR (RT-PCR), and MIF, IFN-γ and TNF-α serum levels were determined by ELISA.

RESULTS

A significant increase of MIF mRNA expression and MIF protein level were found in patients compared to healthy controls. Meanwhile, the increase of IFN-γ and TNF-α serum levels were confirmed. According to the profile of genetic model, a significant association was found of genotypes carrying the -794 CATT 7 or 8 and -173 C risk alleles with susceptibility to active tuberculosis and with a significant increase of MIF, IFN-γ and TNF-α.

CONCLUSIONS

These data suggested a distinct genetic and immunopathogenic basis for tuberculosis at the MIF locus. Serum MIF, IFN-γ and TNF-α profiles distinguish tuberculosis from the more inflammatory phenotype and may play a role in pathogenesis and as biomarkers of active tuberculosis.