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SERUM METABOLIC FINGERPRINTING IDENTIFIED PUTATIVELY ANNOTATED SPHINGANINE ISOMER AS A BIOMARKER OF WOLFRAM SYNDROME Agnieszka Zmyslowska, Michal Ciborowski, Maciej Borowiec, Wojciech Fendler, Karolina Pietrowska, Ewa Parfieniuk, Karolina Antosik, Aleksandra Pyziak, Arleta Waszczykowska, Adam Kretowski, and Wojciech Mlynarski J. Proteome Res., Just Accepted Manuscript • DOI: 10.1021/acs.jproteome.7b00401 • Publication Date (Web): 12 Sep 2017 Downloaded from http://pubs.acs.org on September 14, 2017
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Journal of Proteome Research is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
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Journal of Proteome Research
Running title: Metabolomics in Wolfram syndrome
1 ACS Paragon Plus Environment
Journal of Proteome Research
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SERUM METABOLIC FINGERPRINTING IDENTIFIED PUTATIVELY ANNOTATED SPHINGANINE ISOMER AS A BIOMARKER OF WOLFRAM SYNDROME
Agnieszka Zmyslowska1**, Michal Ciborowski 2**, Maciej Borowiec3**, Wojciech Fendler4 , Karolina Pietrowska2, Ewa Parfieniuk2, Karolina Antosik3, Aleksandra Pyziak1, Arleta Waszczykowska5, Adam Kretowski2,6, Wojciech Mlynarski1* **Equally contributed to this work
1
Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz,
Poland 2
Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
3
Department of Clinical Genetics, Medical University of Lodz, Poland
4
Department of Biostatistics and Translational Medicine, Medical University of Lodz, Poland
5
Department of Ophthalmology and Vision Rehabilitation, Medical University of Lodz,
Poland 6
Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Bialystok,
Bialystok, Poland.
*
Corresponding author:
Wojciech Mlynarski, MD, PhD Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Poland Sporna Str. 36/50, 91-738, Lodz tel. +48 42 6177750, fax: +48 42 6177798 e-mail:
[email protected] 2 ACS Paragon Plus Environment
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Journal of Proteome Research
Abstract: Wolfram syndrome (WFS) is an example of a rare neurodegenerative disease with coexisting endocrine symptoms including diabetes mellitus as the first clinical symptom. Treatment of WFS is still only symptomatic and associated with poor prognosis. Potential markers of disease progression which could be useful for possible intervention trials are not available. Metabolomics has potential to identify such markers. In the present study serum fingerprinting by LC-QTOF-MS was performed in patients with WFS (n=13) and in patients with T1D (n=27). Based on obtained results aminoheptadecanediol (17:0 sphinganine isomer)
(+50%, p=0.02), as the most discriminatory
metabolite, was selected for validation. The 17:0 sphinganine isomer level was determined using the LC-QQQ method in the samples from WFS patients at two time points and compared with samples obtained from patients with T1D (n=24) and healthy controls (n=24). Validation analysis showed higher 17:0 sphinganine isomer level in patients with WFS compared to patients with T1D (p=0.0097) and control group (p
