Macrophage migration inhibitory factor: association of -794 CATT5-8 and -173 G>C polymorphisms with TNF-α in systemic lupus erythematosus

Abstract

Macrophage migration inhibitory factor (MIF) is an upstream immunoregulatory cytokine associated with the pathogenesis of autoimmune inflammatory diseases. There is evidence that MIF functions in a positive feedback loop with TNF-α that could perpetuate the inflammatory process in systemic lupus erythematosus (SLE). In this case-control study we investigated whether commonly occurring functional MIF polymorphisms are associated with SLE as well as with MIF and TNF-α serum levels in a Mexican-Mestizo population. Genotyping of the -794 CATT5-8 (rs5844572) and -173 G>C (rs755622) MIF polymorphisms was performed by PCR and PCR-RFLP, respectively in 186 SLE patients and 200 healthy subjects. MIF and TNF-α serum levels were determined by ELISA. A significant increase of MIF and TNF-α levels was found in SLE patients. According to a genetic model, we found a significant association of genotypes carrying the -794 CATT7 and -173(∗)C risk alleles with susceptibility to SLE and with a significant increase of TNF-α. In conclusion, MIF gene polymorphisms are associated with SLE susceptibility and with an increase of TNF-α serum levels in a Mexican-Mestizo population.

Figure 1

Serum levels by study groups and correlation of MIF and TNF-α. 1a) Comparison of MIF serum levels by study groups; 1b) comparison of TNF-α serum levels by study groups. Data provided in median (p5-p95). U Mann-Whitney test. 1c) Positive correlation of serum levels of MIF and soluble TNF-α . Spearman's correlation test.

Figure 2. MIF and TNF-α concentrations by −794 CATT_5-8 −173 G>C MIF genotypes according to a dominant genetic model

. a) MIF serum levels 10.6 ng/mL (4.80-19.32) vs. 10.7 ng/mL (4.06-20.18) by −794 CATT_5-8 MIF genotypes b) TNF-α serum levels 13.7 pg / mL (8.90-21.51) vs 17.6 pg/mL (10.7-25.48) by −794 CATT_5-8 MIF genotypes. c) MIF serum levels 9.41 ng/mL (4.85-20.18) vs 10.78 ng/mL (4.27-18.81) by −173 G>C MIF genotypes d) TNF-α serum levels 14.01 pg/mL (8.78-21.32) vs 17.09 pg/mL (10.64-24.64) by 173 G>C MIF genotypes. Data provided in median (p25-p75). U Mann-Whitney test.