Metabolomics Profiling for Obstructive Sleep Apnea and Simple Snorers.

Huajun Xu,Yingjun Qian,Xiaojiao Zheng,Jian Guan,Shankai Yin,Yuyu Wang,Hongliang Yi,Aihua Zhao,Wei Jia,Jianyin Zou,Lili Meng

doi:10.1038/srep30958

Huajun Xu, Yingjun Qian + Show 9 more

Open Access

https://doi.org/10.1038/srep30958

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Abstract

Few clinical studies have explored altered urinary metabolite levels in patients with obstructive sleep apnea (OSA). Thus, we applied a metabolomics approach to analyze urinary metabolites in three groups of participants: patients with polysomnography (PSG)-confirmed OSA, simple snorers (SS), and normal subjects. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and gas chromatography coupled with time-of-flight mass spectrometry were used. A total of 21 and 31 metabolites were differentially expressed in the SS and OSA groups, respectively. Patients with OSA had 18 metabolites different from those with SS. Of the 56 metabolites detected among the 3 groups, 24 were consistently higher or lower. A receiver operator curve analysis revealed that the combination of 4-hydroxypentenoic acid, arabinose, glycochenodeoxycholate-3-sulfate, isoleucine, serine, and xanthine produced a moderate diagnostic score with a sensitivity (specificity) of 75% (78%) for distinguishing OSA from those without OSA. The combination of 4-hydroxypentenoic acid, 5-dihydrotestosterone sulfate, serine, spermine, and xanthine distinguished OSA from SS with a sensitivity of 85% and specificity of 80%. Multiple metabolites and metabolic pathways associated with SS and OSA were identified using the metabolomics approach, and the altered metabolite signatures could potentially serve as an alternative diagnostic method to PSG.

Highlights

Metabolomics is a high-sensitivity, high-throughput profiling method with which to study the characteristic changes in low-molecular-weight metabolites in a pathophysiological state
We utilized a combination of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and gas chromatography coupled with time-of-flight mass spectrometry (GC-TOF-MS) to investigate: the metabolic changes occurring during the development of obstructive sleep apnea (OSA), the mechanistic pathways involved in OSA, and candidate metabolite markers useful for diagnosing OSA
Using an integrated MS-based metabolic profiling approach, our study showed that OSA and SS are associated with several altered urinary metabolites

Summary

Introduction

Metabolomics is a high-sensitivity, high-throughput profiling method with which to study the characteristic changes in low-molecular-weight metabolites in a pathophysiological state. The primary aim of such an approach is to explore novel biomarkers and identify physiological and pathological mechanistic processes. The metabolomics analytical platform often includes nuclear magnetic resonance spectroscopy as well as mass spectrometry coupled with gas chromatography or liquid chromatography. A limited number of small-sample-size metabolomics studies have been performed to explore metabolomics profiling and the underlying mechanisms in OSA13–15. We utilized a combination of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and gas chromatography coupled with time-of-flight mass spectrometry (GC-TOF-MS) to investigate: the metabolic changes occurring during the development of OSA, the mechanistic pathways involved in OSA, and candidate metabolite markers useful for diagnosing OSA

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