Abstract
PurposeTo 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.MethodsA 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.ResultsIn 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.ConclusionsIDO2 SNPs and the opposite expression pattern of IDO1 and IDO2 affected IDO activity in Chinese Han TB patients.
Highlights
Indoleamine 2,3-dioxygenase (IDO) is a widely expressed inducible enzyme
IDO1 and IDO2 Single-nucleotide polymorphisms (SNPs) in Chinese Han participants Previous studies reported polymorphisms I91L, A196T, F222S, Q272K, A277D, and S284P in IDO1, which consists of 403 amino acids [22,23,24,25]
For IDO2, SNPs R248W and Y359X were found in both TB patients and healthy controls as in previous reports [6, 26] (Fig. 1; Table 2), which was in agreement with Hardy–Weinberg equilibrium
Summary
IDO comprises two alpha helical domains with a heme group between them. It contributes to the tryptophan (Trp) catabolic pathway and converts Trp to N-formyl kynurenine (Kyn) [1]. The IDO–Kyn pathway is involved in TB by inducing IDO1 expression and activating Trp metabolism [12]. IDO activity has been assessed in serum [13] and pleural fluid [14], and, Cao et al Hereditas (2022) 159:5 with a significant increase in the serum Kyn/Trp ratio, it can be used as a biomarker for TB patients infected with human immunodeficiency virus [15] and for patients with multidrug-resistant TB [16]
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