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Endocrine

06-03-2024 | Xanthine Alkaloid | Original Article

Causality of blood metabolites and metabolic pathways on Graves’ disease and Graves’ ophthalmopathy: a two-sample Mendelian randomization study

Authors: Tingliang Wang, Yun Zhang, Chunjiao Wu, Haiyan Yang, Zuojie Luo

Published in: Endocrine

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Abstract

Objectives

There is ample that metabolic dysregulation is involved in Graves’ disease (GD) and Graves’ ophthalmopathy (GO). Recent studies have identified numerous metabolites associated with GD and GO. However, the causal impact of metabolites on GD and GO remains to be investigated.

Methods

This two-sample Mendelian randomization (MR) analysis investigated the causal relationships between 486 blood metabolites and GD and GO. Sensitivity analysis was also performed to examine heterogeneity and pleiotropy.

Results

MR analysis showed that 9 and 13 metabolites were associated with GD and GO, respectively, each meeting the nominal significance criteria (inverse variance weighted, p < 0.05). Additionally, four metabolic pathways were identified for each condition using network-based MetaboAnalyst 5.0.

Conclusions

The metabolites and pathways discovered in this study could serve as circulating metabolic biomarkers for clinical screening and prevention of GD and GO. They can be also used for further studies on the mechanisms and drug targets in GD and GO.
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Literature
1.
2.
3.
T. Milo et al. Autoimmune thyroid diseases as a cost of physiological autoimmune surveillance. Trends Immunol. 44(5), 365–371 (2023)PubMedCrossRef
4.
J. Cao et al. The risk factors for Graves’ ophthalmopathy. Graefes Arch. Clin. Exp. Ophthalmol. 260(4), 1043–1054 (2022)PubMedCrossRef
5.
L. Bartalena et al. Epidemiology, Natural History, Risk Factors, and Prevention of Graves’ Orbitopathy. Front Endocrinol. 11, 615993 (2020)CrossRef
6.
R. Ma et al. Insights Into Ferroptosis: Targeting Glycolysis to Treat Graves’ Orbitopathy. J. Clin. Endocrinol. Metab. 107(7), 1994–2003 (2022)PubMedCrossRef
7.
X. Chen et al. Influence of 4-week or 12-week glucocorticoid treatment on metabolic changes in patients with active moderate-to-severe thyroid-associated ophthalmopathy. Clin. Transl. Sci. 14(5), 1734–1746 (2021)PubMedPubMedCentralCrossRef
8.
H.O. Ueland et al. Systemic Activation of the Kynurenine Pathway in Graves Disease With and Without Ophthalmopathy. J. Clin. Endocrinol. Metab. 108(6), 1290–1297 (2023)PubMedPubMedCentralCrossRef
9.
S.K. Byeon et al. Lipidomic differentiation of Graves’ ophthalmopathy in plasma and urine from Graves’ disease patients. Anal. Bioanal. Chem. 410(27), 7121–7133 (2018)PubMedCrossRef
10.
D.Y. Ji et al. Comparative assessment of Graves’ disease and main extrathyroidal manifestation, Graves’ ophthalmopathy, by non-targeted metabolite profiling of blood and orbital tissue. Sci. Rep. 8(1), 9262 (2018)ADSPubMedPubMedCentralCrossRef
11.
X. Zhang et al. Exploring blood metabolites and thyroid disorders: a bidirectional mendelian randomization study. Front Endocrinol. 14, 1270336 (2023)CrossRef
12.
B.L. Pierce et al. Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators. Am. J. Epidemiol. 178(7), 1177–1184 (2013)PubMedPubMedCentralCrossRef
13.
J. Bowden et al. Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 40(4), 304–314 (2016)PubMedPubMedCentralCrossRef
14.
15.
A.F. Schmidt et al. Mendelian randomization with Egger pleiotropy correction and weakly informative Bayesian priors. Int J. Epidemiol. 47(4), 1217–1228 (2018)PubMedCrossRef
16.
17.
Y. Chang et al. Tryptophan 2,3-dioxygenase 2 plays a key role in regulating the activation of fibroblast-like synoviocytes in autoimmune arthritis. Br. J. Pharm. 179(12), 3024–3042 (2022)CrossRef
18.
19.
Y. Park et al. Kynurenine pathway can be a potential biomarker of fatigue in primary Sjögren’s syndrome. Clin. Exp. Rheumatol. 41(12), 2363–2370 (2023)PubMed
20.
21.
S.M.T. Isık et al. Relationship of tryptophan metabolites with the type and severity of multiple sclerosis. Mult. Scler. Relat. Disord. 77, 104898 (2023)PubMedCrossRef
22.
A. Krupa et al. The Kynurenine Pathway-New Linkage between Innate and Adaptive Immunity in Autoimmune Endocrinopathies. Int J. Mol. Sci. 22(18), 9879 (2021)PubMedPubMedCentralCrossRef
23.
24.
C. Chen et al. Metabolomic profiling reveals amino acid and carnitine alterations as metabolic signatures in psoriasis. Theranostics 11(2), 754–767 (2021)PubMedPubMedCentralCrossRef
25.
X. Cheng et al. Long-Chain Acylcarnitines Induce Senescence of Invariant Natural Killer T Cells in Hepatocellular Carcinoma. Cancer Res. 83(4), 582–594 (2023)PubMedCrossRef
26.
U. Wenzel et al. Increased mitochondrial palmitoylcarnitine/carnitine countertransport by flavone causes oxidative stress and apoptosis in colon cancer cells. Cell Mol. Life Sci. 62(24), 3100–3105 (2005)PubMedCrossRef
27.
M.C. Mutomba et al. Regulation of the activity of caspases by L-carnitine and palmitoylcarnitine. FEBS Lett. 478(1-2), 19–25 (2000)PubMedCrossRef
28.
B. Kisiel et al. Polymorphism of the oestrogen receptor beta gene (ESR2) is associated with susceptibility to Graves’ disease. Clin. Endocrinol. 68(3), 429–434 (2008)CrossRef
29.
30.
A.M. FitzPatrick, Is Estrogen a Missing Culprit in Thyroid Eye Disease? Sex Steroid Hormone Homeostasis Is Key to Other Fibrogenic Autoimmune Diseases - Why Not This One? Front Immunol. 13, 898138 (2022)PubMedPubMedCentralCrossRef
31.
H.B. Burch et al. Superoxide radical production stimulates retroocular fibroblast proliferation in Graves’ ophthalmopathy. Exp. Eye Res 65(2), 311–316 (1997)PubMedCrossRef
32.
T. Mano et al. Changes in free radical scavengers and lipid peroxide in thyroid glands of various thyroid disorders. Horm. Metab. Res 29(7), 351–354 (1997)PubMedCrossRef
33.
R. Du et al. Metabolic features of orbital adipose tissue in patients with thyroid eye disease. Front. Endocrinol. 14, 1151757 (2023)CrossRef
34.
J. Zhou et al. Detection and Correlation Analysis of Serum Uric Acid in Patients with Thyroid-Associated Ophthalmopathy. Comput. Math. Methods Med. 2022, 8406834 (2022)PubMedPubMedCentralCrossRef
35.
N.F. Marques et al. Guanosine Protects Striatal Slices Against 6-OHDA-Induced Oxidative Damage, Mitochondrial Dysfunction, and ATP Depletion. Neurotox. Res. 35(2), 475–483 (2019)PubMedCrossRef
36.
B. Bellaver et al. Guanosine inhibits LPS-induced pro-inflammatory response and oxidative stress in hippocampal astrocytes through the heme oxygenase-1 pathway. Purinergic. Signal 11(4), 571–580 (2015)PubMedPubMedCentralCrossRef
37.
L.E. Bettio et al. Guanosine prevents behavioral alterations in the forced swimming test and hippocampal oxidative damage induced by acute restraint stress. Pharm. Biochem. Behav. 127, 7–14 (2014)CrossRef
38.
39.
C.C. Tsai et al. Increased oxidative DNA damage, lipid peroxidation, and reactive oxygen species in cultured orbital fibroblasts from patients with Graves’ ophthalmopathy: evidence that oxidative stress has a role in this disorder. Eye 24(9), 1520–1525 (2010)PubMedCrossRef
40.
J. Liu et al. Serum Metabolomic Patterns in Patients with Autoimmune Thyroid Disease. Endocr. Pr. 26(1), 82–96 (2020)CrossRef
41.
T.J. Smith, Insulin-Like Growth Factor Pathway and the Thyroid. Front Endocrinol. 12, 653627 (2021)CrossRef
42.
P. Castrogiovanni et al. Effects of high-tryptophan diet on pre- and postnatal development in rats: a morphological study. Eur. J. Nutr. 53(1), 297–308 (2014)PubMedCrossRef
43.
F. Liang et al. Tobacco carcinogen induces tryptophan metabolism and immune suppression via induction of indoleamine 2,3-dioxygenase 1. Signal Transduct. Target Ther. 7(1), 311 (2022)PubMedPubMedCentralCrossRef
44.
L. Zhu et al. Advancing metabolic networks and mapping updated urinary metabolic fingerprints after exposure to typical carcinogenic heterocyclic aromatic amines. Environ. Pollut. 319, 120936 (2023)PubMedCrossRef
45.
R.D. Michalek et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J. Immunol. 186(6), 3299–3303 (2011)PubMedCrossRef
46.
Z. Wu et al. Purine metabolism-related genes and immunization in thyroid eye disease were validated using bioinformatics and machine learning. Sci. Rep. 13(1), 18391 (2023)ADSPubMedPubMedCentralCrossRef
Metadata
Title
Causality of blood metabolites and metabolic pathways on Graves’ disease and Graves’ ophthalmopathy: a two-sample Mendelian randomization study
Authors
Tingliang Wang
Yun Zhang
Chunjiao Wu
Haiyan Yang
Zuojie Luo
Publication date
06-03-2024
Publisher
Springer US
Published in
Endocrine
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-024-03761-z
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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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