Association of interferon-gamma +874(T/A) single nucleotide polymorphism with the rate of tryptophan catabolism in healthy individuals

Abstract Mechanisms induced by tryptophan (trp) catabolism are important in the regulation of both normal and pathogenetic immune responses. The key enzyme is indoleamine-pyrrole 2,3-dioxygenase (EC 1.13.11.42) (IDO) which converts trp to kynurenine (kyn), the main toxic metabolite. It is known that interferon-gamma (IFN-gamma) is able to activate IDO. We wanted to analyse whether the strength of this mechanism would be under genetic control. To this end, we analysed the IFN-gamma+874(T/A) genotypes, which are known to have an effect on IFN-gamma production, of 309 healthy blood donors and correlated these to the levels of trp and kyn in their blood. The data obtained demonstrate that the presence of the high producer T allele was associated with increased IDO activity (i.e. elevated kyn and kyn/trp levels), but this effect was observed only in females. These data show that trp catabolism is genetically controlled by the IFN-gamma gene and may thus be operative in those disease conditions associated with the polymorphisms of the IFN-gamma gene.