Oxidative stress-mediated (sex-specific) loss of protection against type-2 diabetes by macrophage migration inhibitory factor (MIF)-173G/C polymorphism

Background: The archetypical yet atypical cytokine macrophage migration inhibitory factor (MIF) fulfills pleiotropic immune functions in inflammatory diseases. Evidence emerging from both expression and functional studies implicates MIF in various aspects of cardiovascular diseases. We aimed to determine the covariates of MIF-173G/C polymorphism and its influence on type-2 diabetes risk in a sample representative of middle-aged Turks.

Methods: Randomly selected 2250 Turkish adults (mean age; 49.7±11.9, 48.5% male) were genotyped for -173G/C polymorphism using hybridization probes in Real-Time PCR LC480 device.

Results: The MIF-173CC genotype prevailed in 3.7% in men and 2.9% in women. C-allele carriage was associated linearly with wider waist girth, independently of fasting glucose, and was further related to higher apolipoprotein B (apoB) (p<0.05) in men, but not women. Logistic regression analysis showed the C-allele carriage to tend to predict new-onset diabetes (RR 1.51; [95% CI 0.98; 2.32]), additively to age and fasting glucose in men, but not in women. In contrast, risk for established (baseline) diabetes mellitus was lower (OR=0.49, 95% Cl 0.26-0.93, p=0.03) in heterozygotes, after adjustment for atherogenic dyslipidemia and other confounders.

Conclusion: MIF-173GC polymorphism independently contributes to abdominal obesity and is related to apoB concentrations apparently in men alone. Tendency of the -173C-allele carriage to predict new-onset diabetes independently was also confined to men. These gender-modulated associations suggest novel gene-gender-environmental interactions originating from a proinflammatory state.