Genetic variants and serum levels analysis of indoleamine 2,3-dioxygenase in Behcet’s disease

Purpose: Behcet’s Disease (BD) is a multisystemic disorder with an unknown etiology, having the highest prevalence rates in Turkey. Genetic factors, including familial aggregation, contribute significantly to its pathogenesis. Indoleamine 2,3-dioxygenase (IDO), a key enzyme in tryptophan metabolism, has been implicated in immune regulation and inflammation. IDO activity is believed to play a role in maintaining immune homeostasis by regulating T cell responses and promoting immune tolerance. Herein, this study aimed to investigate the association between IDO gene polymorphisms, serum IDO levels, and BD susceptibility in ninety BD patients and 52 healthy controls. Methods: Genomic DNA was extracted from the patient’s blood by using DNA isolation kit, and single nucleotide gene polymorphisms for IDO (rs7820268, rs10108662) and IDO-2 (rs4503083) were determined using RT-PCR together with the melting curve analysis method using fluorescence resonance energy transfer probs. Serum samples were collected for IDO and IDO-2 measurement using enzyme-linked immunosorbent assay (ELISA). In addition, clinical manifestations of BD such as oral ulcer, genital ulcer, uveitis, and neurological involvement were compared with serum IDO and IDO-2 levels of patients. Results: Having been in Hardy-Weinberg equilibrium of all allele and genotype frequencies of patients and controls, statistical analyses revealed no significant differences in gene polymorphisms of IDO and IDO-2. On the other hand, serum IDO and IDO-2 levels were significantly lower in BD patients (p&lt;0.001 and p&lt;0.001, respectively), and a strong correlation was identified between IDO and IDO-2 levels (r=0.920, p&lt;0.001). Furthermore, only serum IDO-2 levels were significantly lower in patients with a neuro-Behçet group compared to those without neurological involvement seen groups (n=7 and n=83 respectively, p&lt;0.001). Conclusion: While no significant differences were found in IDO gene polymorphisms between patients and healthy controls, serum IDO levels were notably lower in BD patients. This suggests a potential dysregulation of IDO activity in BD, possibly contributing to the proinflammatory immune response observed in the disease.<br>