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. 2022 Jan 19;159(1):5.
doi: 10.1186/s41065-022-00219-y.

Single-nucleotide polymorphisms and activities of indoleamine 2,3-dioxygenase isoforms, IDO1 and IDO2, in tuberculosis patients

Tingming Cao #  1   2 , Guangming Dai #  1   2 , Hongqian Chu  1   2 , Chengcheng Kong  1   2 , Huijuan Duan  1   2 , Na Tian  1   2 , Zhaogang Sun  3   4
Affiliations

Single-nucleotide polymorphisms and activities of indoleamine 2,3-dioxygenase isoforms, IDO1 and IDO2, in tuberculosis patients

Tingming Cao et al. Hereditas. .

Abstract

Purpose: To explore the role and effects of the single-nucleotide polymorphisms (SNPs) of the two functionally related indoleamine 2,3-dioxygenase (IDO) isoforms on IDO activity in the Chinese Han ethnic population.

Methods: A total of 151 consecutive patients of Chinese Han ethnicity (99 men and 52 women; average age 51.92 ± 18.26 years) with pulmonary TB admitted to Beijing Chest Hospital between July 2016 and February 2017 were enrolled in the study. The serum levels of tryptophan (Trp) and its metabolites, IDO1 and IDO2 mRNA levels, and the relationship of IDO1 and IDO2 SNPs with the serum Kyn/Trp ratio in TB patients and healthy controls were examined by LC/ESI-MS/MS analysis. Genomic DNA was isolated from whole blood, and the PCR products were sequenced and analyzed.

Results: In Chinese Han participants, only IDO2 had SNPs R248W and Y359X that affected IDO activity, as determined by the serum Kyn/Trp ratio. IDO1 and IDO2 mRNA levels were inversely related in TB patients and healthy controls.

Conclusions: IDO2 SNPs and the opposite expression pattern of IDO1 and IDO2 affected IDO activity in Chinese Han TB patients.

Keywords: Indoleamine 2,3-dioxygenase; Kynurenine; Single-nucleotide polymorphism; Tryptophan.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Sanger sequence electropherograms of R248W and Y359X and the position of R248W and Y359X in the predicted 3D structure. (a) Three IDO2 genotypes were found in R248W and Y359X: wild type, heterocigoto type, and homocigoto type; (b) Mutations in the predicted 3D structure of IDO2 (red arrows). Structure prediction using the SWISS-MODEL server showed that IDO1 and IDO2 formed dimers. Interaction values of binding free energy (− 12.75 kcal/mol) and dissociation constant (4.50 e− 10 M) were estimated using the PPA-Pred2 online software (Protein-Protein Affinity Predictor; https://www.iitm.ac.in/bioinfo/PPA_Pred/prediction.html)
Fig. 2
Fig. 2
IDO1 and IDO2 mRNA levels in healthy controls, TB patients, and M. tb H37Rv-infected BALB/c mice. a IDO1 and IDO2 mRNA levels in TB patients and healthy controls grouped by IDO2 genotypes; (b) IDO1 and IDO2 mRNA levels in M. tb H37Rv-infected BALB/c mice with four in each group. The mice were infected with 300 colony-forming units by the aerosol route
Fig. 3
Fig. 3
Quantitative standard curves by chromatographic analysis (LC/ESI–MS/MS). A Serum Trp; (B) Serum Kyn; (C) Serum Kyn/Trp ratio in TB patients and healthy controls. *P < 0.05
See this image and copyright information in PMC

References

    1. Sugimoto H, Oda S, Otsuki T, Hino T, Yoshida T, Shiro Y. Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase. Proc Natl Acad Sci U S A. 2006;103(8):2611–2616. doi: 10.1073/pnas.0508996103. - DOI - PMC - PubMed
    1. Cervenka I, Agudelo LZ, Ruas JL. Kynurenines: tryptophan’s metabolites in exercise, inflammation, and mental health. Science. 2017;357(6349):eaaf9794. doi: 10.1126/science.aaf9794. - DOI - PubMed
    1. Platten M, Nollen EAA, Röhrig UF, Fallarino F, Opitz CA. Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond. Nat Rev Drug Discov. 2019;18(5):379–401. doi: 10.1038/s41573-019-0016-5. - DOI - PubMed
    1. Metz R, Smith C, DuHadaway JB, Chandler P, Baban B, Merlo LM, Pigott E, Keough MP, Rust S, Mellor AL, Mandik-Nayak L, Muller AJ, Prendergast GC. IDO2 is critical for IDO1-mediated T-cell regulation and exerts a non-redundant function in inflammation. Int Immunol. 2014;26(7):357–367. doi: 10.1093/intimm/dxt073. - DOI - PMC - PubMed
    1. Merlo LMF, Pigott E, DuHadaway JB, Grabler S, Metz R, Prendergast GC, Mandik-Nayak L. IDO2 is a critical mediator of autoantibody production and inflammatory pathogenesis in a mouse model of autoimmune arthritis. J Immunol. 2014;192(5):2082–2090. doi: 10.4049/jimmunol.1303012. - DOI - PMC - PubMed