Single nucleotide polymorphisms in cytokine MIF gene promoter region are closely associated with human susceptibility to tuberculosis in a southwestern province of China

Abstract

The gene encoding macrophage migration inhibitory factor (MIF) has been proposed as candidate tuberculosis (TB) susceptibility gene. In order to elucidate whether MIF gene variants are associated with susceptibility to retreatment cases of TB, and prevent drug-resistant TB prevalence, we conducted a study based on paired human population data. MIF −173 G/C single nucleotide polymorphisms (rs755622) were genotyped using polymerase chain reaction-restriction fragment length polymorphism. MIF levels were detected with enzyme-linked immunosorbent assay. Association analysis of polymorphism to TB showed that distribution of MIF −173 genotypes (GC+CC) was significantly higher in total cases of TB than in the controls. Statistically significant differences of frequencies for MIF −173 (GG vs. GC+CC) were demonstrated when comparing total cases of TB, new cases of TB, and retreatment cases of TB to controls, respectively. In contrast, the frequencies of MIF −173 (GG vs. GC+CC) demonstrated no difference between new cases of TB and retreatment cases of TB. Association analysis of MIF protein concentrations to TB indicated that MIF concentration is significantly higher in total cases of TB, new cases of TB, and retreatment cases of TB than in controls (P<0.01). In summary, our results demonstrated that MIF gene −173 G/C single nucleotide polymorphisms implicate in genetic susceptibility to TB, and GC+CC of MIF −173 site increases the risk of TB. We also found that no correlation between −173 G/C single nucleotide polymorphism and retreatment cases of TB in Yunnan Province population of China.