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Comparative assessment of Graves' disease and main extrathyroidal manifestation, Graves' ophthalmopathy, by non-targeted metabolite profiling of blood and orbital tissue

 Dong Yoon Ji  ;  Se Hee Park  ;  Soo Jin Park  ;  Kyoung Heon Kim  ;  Cheol Ryong Ku  ;  Dong Yeob Shin  ;  Jin Sook Yoon  ;  Do Yup Lee  ;  Eun Jig Lee 
 Scientific Reports, Vol.8(1) : 9262, 2018 
Journal Title
 Scientific Reports 
Issue Date
Graves' disease (GD) is an autoimmune disorder that causes the overproduction of thyroid hormones and consequent cascade of systemic metabolism dysfunction. Moreover, Graves' ophthalmopathy (GO) is the main extrathyroidal manifestation of Graves' disease (GD). The goal of the study was to identify metabolic signatures in association with diagnostic biomarkers of GD without GO and GO, respectively. Ninety metabolites were profiled and analyzed based on a non-targeted primary metabolite profiling from plasma samples of 21 GD patients without GO, 26 subjects with GO, and 32 healthy subjects. Multivariate statistics showed a clear discrimination between healthy controls and disease group (R2Y = 0.518, Q2 = 0.478) and suggested a biomarker panel consisting of 10 metabolites. Among them, most of metabolites showed the positive association with the levels of thyrotropin receptor antibodies. With combination of proline and 1,5-anhydroglucitol, which were identified as GO-specific modulators, the re-constructed biomarker model greatly improved the statistical power and also facilitated simultaneous discrimination among healthy control, GO, and GD without GO groups (AUC = 0.845-0.935). Finally, the comparative analysis of tissue metabolite profiles from GO patients proposed putative metabolic linkage between orbital adipose/connective tissues and the biofluidic consequences, in which fumarate, proline, phenylalanine, and glycerol were coordinately altered with the blood metabolites.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
구철룡(Ku, Cheol Ryong) ORCID logo https://orcid.org/0000-0001-8693-9630
박세희(Park, Se Hee)
신동엽(Shin, Dong Yeob) ORCID logo https://orcid.org/0000-0003-1048-7978
윤진숙(Yoon, Jin Sook) ORCID logo https://orcid.org/0000-0002-8751-9467
이은직(Lee, Eun Jig) ORCID logo https://orcid.org/0000-0002-9876-8370
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