Metabolite Genome-Wide Association Study for Indoleamine 2,3-Dioxygenase Activity Associated with Chronic Kidney Disease

Kim, Hyerim; Jin, Hyun‐Seok; Eom, Yong‐Bin

doi:10.3390/genes12121905

Cited by 4 publications

(5 citation statements)

References 59 publications

(63 reference statements)

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“…A genome-wide association study revealed a potential genetic connection between IDO activity and CKD, and Zhang et al discovered elevated IDO activity in individuals with type 2 diabetic nephropathy. 38 , 39 Antagonizing IDO was effective in reducing renal fibrosis during CKD, possibly due to the TGF-β-mediated tubular epithelial-mesenchymal transition. 40 , 41 The metabolism of tryptophan by IDO also has a direct or indirect link to atherogenesis, and Walker et al discovered that inhibiting IDO activity could potentially decrease thrombosis in CKD.…”

Section: Discussionmentioning

confidence: 94%

Prediction Model for Early-Stage CKD Using the Naples Prognostic Score and Plasma Indoleamine 2,3-dioxygenase Activity

Hong,

Zheng,

Shi

et al. 2024

JIR

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Purpose Changes in inflammation, immunity, and nutritional status can promote the development of chronic kidney disease (CKD), and the Naples prognostic score (NPS) reflects changes in these three general clinical parameters. Indoleamine 2.3-dioxygenase (IDO) can block the function of inflammatory cells and inhibit the production of inflammatory cytokines. We examined use of the NPS and IDO activity to predict early-stage CKD. Patients and Methods Clinical and demographic parameters and the NPS were recorded for 47 CKD patients and 30 healthy controls. A one-way ANOVA or the rank sum test was used to compare variables in the different groups. Spearman or Pearson correlation coefficients were calculated, and logistic regression was used to identify significant factors. Receiver operating characteristic (ROC) analysis was also performed. Results The NPS had a positive correlation with plasma IDO activity and IDO activity was lowest in controls, and increased with CKD stage. ROC analysis indicated that NPS had an area under the curve (AUC) of 0.779 when comparing controls with all CKD patients. A prediction model for CKD (−4.847 + [1.234 × NPS] + [6.160 × plasma IDO activity]) demonstrated significant differences between controls and patients with early-stage CKD, and for patients with different stages of CKD. This model had AUC values of 0.885 (control vs CKD1–4), 0.876 (control vs CKD2), 0.818 (CKD2 vs CKD3), and 0.758 (CKD3 vs CKD4). Conclusion A prediction model based on the NPS and IDO provided good to excellent predictions of early-stage CKD.

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Section: Discussionmentioning

confidence: 94%

Prediction Model for Early-Stage CKD Using the Naples Prognostic Score and Plasma Indoleamine 2,3-dioxygenase Activity

Hong,

Zheng,

Shi

et al. 2024

JIR

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“…Various populations, including Koreans [28], have provided evidence to support the connection between IDO activity and CKD [7,13,14]. We have recently conducted an integrated metabolome and genome association analysis to identify genetic markers for detecting CKD in its early stages [15]. However, the previous study that focused on IDO activity had a limitation, as the correlation with CKD was moderately low.…”

Section: Discussionmentioning

confidence: 99%

“…IDO was also associated with diabetic nephropathy [12] and renal fibrosis [11]. Furthermore, several studies have demonstrated the association between CKD and IDO activity [7,[13][14][15].…”

Section: Introductionmentioning

confidence: 99%

“…CKD has been proven to be a complex disease with high heritability [2,19]. Hence, we hypothesized that genetic factors might play a role in altering IDO activity and through a combining genomics and metabolomics data analysis of a Korean cohort, we have recently identified multiple loci linked to IDO activity associated with CKD [15]. However, since our previous study had a narrow focus on IDO activity, the statistical significance of CKD and eGFR was paid less attention.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Genetic Markers Linked to The Activity of Indoleamine 2,3-Dioxygenase and Kidney Function

2023

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Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme belonging to the kynurenine pathway. IDO activity has been suggested as a potential biomarker for early diagnosis of chronic kidney disease (CKD). The aim of this study was to perform coincident association analysis to gain genetic insights into the correlation between IDO activity and CKD. This study evaluated the association between IDO activity and CKD using the Korea Association REsource (KARE) cohort. Logistic and linear regression were used to analyze CKD and quantitative phenotypes such as IDO and estimated glomerular filtration rate (eGFR). Our results identified 10 single nucleotide polymorphisms (SNPs) that were coincidently associated with both IDO and CKD (p < 0.001). Among them, rs6550842, rs77624055, and rs35651150 were selected as potential candidates after excluding SNPs with insufficient evidence for having an association with IDO or CKD. Further expression quantitative trait loci (eQTL) analysis for variants at selected loci showed that rs6550842 and rs35651150 significantly affected the expression of NKIRAS1 and SH2D4A genes in human tissues, respectively. Additionally, we highlighted that the NKIRAS1 and BMP6 genes were correlated with IDO activity and CKD through signaling pathways associated with inflammation. Our data suggest that NKIRAS1, SH2D4A, and BMP6 were potential causative genes affecting IDO activity and CKD through integrated analysis. Identifying these genes could aid in early detection and treatment by predicting the risk of CKD associated with IDO activity.

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“…, 2022 ), psoriasis ( Vecellio et al. , 2021 ), and chronic kidney disease (CKD) ( Kim et al. , 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Interaction of the sorting nexin 25 homologue Snazarus with Rab11 balances endocytic and secretory transport and maintains the ultrafiltration diaphragm in nephrocytes

Maruzs

Feil-Börcsök

Lakatos

et al. 2023

MBoC

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Proper balance of exocytosis and endocytosis is important for the maintenance of plasma membrane lipid and protein homeostasis. This is especially critical in human podocytes and the podocyte-like Drosophila nephrocytes that both use a delicate diaphragm system with evolutionarily conserved components for ultrafiltration. Here we show that the sorting nexin 25 homolog Snazarus (Snz) binds to Rab11 and localizes to Rab11-positive recycling endosomes in Drosophila nephrocytes, unlike in fat cells where it is present in plasma membrane/lipid droplet/ER contact sites. Loss of Snz leads to redistribution of Rab11 vesicles from the cell periphery and increases endocytic activity in nephrocytes. These changes are accompanied by defects in diaphragm protein distribution that resemble those seen in Rab11 gain-of-function cells. Of note, co-overexpression of Snz rescues diaphragm defects in Rab11 overexpressing cells, whereas snz knockdown in Rab11 overexpressing nephrocytes or simultaneous knockdown of snz and tbc1d8b encoding a Rab11 GAP lead to massive expansion of the lacunar system that contains mislocalized diaphragm components: Sns and Pyd/ZO-1. We find that loss of Snz enhances while its overexpression impairs secretion, which, together with genetic epistasis analyses, suggest that Snz counteracts Rab11 to maintain the diaphragm via setting the proper balance of exocytosis and endocytosis. [Media: see text] [Media: see text] [Media: see text]

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Metabolite Genome-Wide Association Study for Indoleamine 2,3-Dioxygenase Activity Associated with Chronic Kidney Disease

Cited by 4 publications

References 59 publications

Prediction Model for Early-Stage CKD Using the Naples Prognostic Score and Plasma Indoleamine 2,3-dioxygenase Activity

Prediction Model for Early-Stage CKD Using the Naples Prognostic Score and Plasma Indoleamine 2,3-dioxygenase Activity

Identification of Genetic Markers Linked to The Activity of Indoleamine 2,3-Dioxygenase and Kidney Function

Interaction of the sorting nexin 25 homologue Snazarus with Rab11 balances endocytic and secretory transport and maintains the ultrafiltration diaphragm in nephrocytes

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