TNF-α and IFN-γ gene variation and genetic susceptibility to type 1 diabetes and its microangiopathic complications

BACKGROUND: TNF-α has accelerating role in development of type 1 diabetes. Although an immunosupressor function and leading protecting role in T1DM also has been claimed for this pro-inflammatory cytokine. Over-expression of pro-inflammatory and type 1 cytokines (Th1, like IFN-γ) drive insulitis toward the destructive form that leads to type 1 diabetes (T1DM). Among type 1 cytokines only IFN-γ has been detectable in the islet β cells. In deletion studies IFN-γ was also the only Th1 cytokine for which its ablation or blockade caused delayed or decreased incidence of T1DM. METHODS: Functional polymorphisms of TNF-α at position -308*G/A and at position +874*T/A of IFN-γ gene were employed as markers and the comparative distribution of derived genotypes/alleles were assessed in 248 British Caucasian T1DM patients and 118 healthy controls. RESULTS: There was no significant association between IFN-γ gene polymorphism and T1DM or the diabetic complication triad. There was a marginal association between TNF-α –308*G/A polymorphism in nephropaths (vs healthy controls) (p = 0.06), which its insignificancy may be due to survivor factor. No significant association was evident between the genotype/allele of the applied marker and T1DM or diabetic complication triad. CONCLUSION: Our results are in contrast with previous reports suggesting that these polymorphisms are not related to T1DM. This study also underlines the importance of replication of association studies to confirm the previous interpretation.