Maekawa, M;
Jinnoh, I;
Narita, A;
Iida, T;
Saigusa, D;
Iwahori, A;
Nittono, H;
... Mano, N; + view all
(2019)
Development of a simultaneous analytical method for five conjugated cholesterol metabolites in urine and investigation of their performance as diagnostic markers for Niemann-Pick disease type C.
Journal of Lipid Research
10.1194/jlr.M093971.
(In press).
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Abstract
Niemann-Pick disease type C (NPC) is an autosomal recessive disorder characterized by progressive nervous degeneration. Because of the diversity of clinical symptoms and onset age, the diagnosis of this disease is difficult. Therefore, biomarker tests have attracted significant attention for earlier diagnostics. In this study, we developed a simultaneous analysis method for five urinary conjugated cholesterol metabolites, which are potential diagnostic biomarkers for a rapid, convenient, and noninvasive chemical diagnosis, using liquid chromatography/tandem mass spectrometry (LC/MS/MS). By the method, their urinary concentrations were quantified and the NPC diagnostic performances were evaluated. The developed LC/MS/MS method showed high accuracy and and satisfied all analytical method validation criteria. Analyzing the urine of healthy controls and patients with NPC, three of five urinary conjugated cholesterol metabolites concentrations corrected by urinary creatinine were significantly higher in the patients with NPC. As a result of receiver operating characteristics analysis, the urinary metabolites might have excellent diagnostic marker performance. 3β-sulfooxy-7β-hydroxy-5-cholenoic acid showed particularly excellent diagnostic performance with both 100% clinical sensitivity and specificity, suggesting that it is a useful NPC diagnostic marker. The urinary conjugated cholesterol metabolites exhibited high NPC diagnostic marker performance and could be used for NPC diagnosis.
| Type: | Article |
|---|---|
| Title: | Development of a simultaneous analytical method for five conjugated cholesterol metabolites in urine and investigation of their performance as diagnostic markers for Niemann-Pick disease type C |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1194/jlr.M093971 |
| Publisher version: | https://doi.org/10.1194/jlr.M093971 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Biomarkers, Cholesterol/Metabolism, Conjugated cholesterol metabolites, Diagnostic tools, Mass spectrometry, Niemann-Pick disease, Niemann-Pick disease type C, Urine |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10083436 |
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