Identification of a Reliable Biomarker Profile for the Diagnosis of Gaucher Disease Type 1 Patients Using a Mass Spectrometry-Based Metabolomic Approach
Autor: | Georges-Etienne Rivard, Christiane Auray-Blais, François Mercier, Iskren Menkovic, Michel Boutin, Abdulfatah Alayoubi |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Adult
Male Phosphorylcholine Disease Gaucher disease Mass spectrometry Tandem mass spectrometry Sensitivity and Specificity Catalysis Article Inorganic Chemistry lcsh:Chemistry Young Adult Metabolomics N-palmitoyl-O-phosphocholineserine Sphingosine glucosylsphingosine (lyso-Gb1) Statistical analyses Humans Physical and Theoretical Chemistry lyso-Gb1 analogs Molecular Biology lcsh:QH301-705.5 Spectroscopy Chromatography High Pressure Liquid plasma Aged mass spectrometry Plasma samples Chemistry Organic Chemistry Psychosine biomarkers sphingosylphosphorylcholine General Medicine Middle Aged Prognosis metabolomics Computer Science Applications Early Diagnosis lcsh:Biology (General) lcsh:QD1-999 Case-Control Studies Cancer research Biomarker (medicine) Female Glucocerebrosidase |
Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 7869, p 7869 (2020) International Journal of Molecular Sciences Volume 21 Issue 21 |
ISSN: | 1661-6596 1422-0067 |
Popis: | Gaucher disease (GD) is a rare autosomal recessive multisystemic lysosomal storage disorder presenting a marked phenotypic and genotypic variability. GD is caused by a deficiency in the glucocerebrosidase enzyme. The diagnosis of GD remains challenging because of the large clinical spectrum associated with the disease. Moreover, GD biomarkers are often not sensitive enough and can be subject to polymorphic variations. The main objective of this study was to perform a metabolomic study using an ultra-performance liquid chromatography system coupled to a time-of-flight mass spectrometer to identify novel GD biomarkers. Following the analysis of plasma samples from patients with GD, and age- and gender-matched control samples, supervised statistical analyses were used to find the best molecules to differentiate the two groups. Targeted biomarkers were structurally elucidated using accurate mass measurements and tandem mass spectrometry. This metabolomic study was successful in highlighting seven biomarkers associated with GD. Fragmentation tests revealed that these latter biomarkers were lyso-Gb1 (glucosylsphingosine) and four related analogs (with the following modifications on the sphingosine moiety: -C2H4, -H2, -H2+O, and +H2O), sphingosylphosphorylcholine, and N-palmitoyl-O-phosphocholineserine. Based on the plasma biomarker distribution, we suggest the evaluation of this GD biomarker profile, which might facilitate early diagnosis, monitoring, and follow-up of patients. |
Databáze: | OpenAIRE |
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