Evaluation of plasma cholestane-3 β,5 α,6 β -triol and 7-ketocholesterol in inherited disorders related to cholesterol metabolism

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Abstract

Oxysterols are intermediates of cholesterol metabolism and are generated from cholesterol via either enzymatic or nonenzymatic pathways under oxidative stress conditions. Cholestan-3β, 5α, 6β-triol (c-triol) and 7-ketocholesterol (7-KC) have been proposed as new biomarkers for the diagnosis of Niemann-Pick type C (NP-C) disease, representing an alternative tool to the invasive and time-consuming method of fibroblast filipin test. To test the efficacy of plasma oxysterol determination for the diagnosis of NP-C, we systematically screened oxysterol levels in patients affected by different inherited disorders related with cholesterol metabolism, which included Niemann-Pick type B (NP-B) disease, lysosomal acid lipase (LAL) deficiency, Smith-Lemli-Opitz syndrome (SLOS), congenital familial hypercholesterolemia (FH), and sitosterolemia (SITO). As expected, NP-C patients showed significant increase of both C-triol and 7-KC. Strong increase of both oxysterols was observed in NP-B and less pronounced in LAL deficiency. In SLOS, only 7-KC was markedly increased, whereas in both FH and in SITO, oxysterol concentrations were normal. Interestingly, in NP-C alone, we observed that plasma oxysterols correlate negatively with patient's age and positively with serum total bilirubin, suggesting the potential relationship between oxysterol levels and hepatic disease status. Our results indicate that oxysterols are reliable and sensitive biomarkers of NP-C.-Boenzi, S., F. Deodato, R. Taurisano, B. M. Goffredo, C. Rizzo, and C. Dionisi-Vici. Evaluation of plasma cholestane-3β, 5α, 6β-triol and 7-ketocholesterol in inherited disorders related to cholesterol metabolism.

Original languageEnglish
Pages (from-to)361-367
Number of pages7
JournalJournal of Lipid Research
Volume57
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

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Metabolism
Cholesterol
Sterol Esterase
Plasmas
Biomarkers
Smith-Lemli-Opitz Syndrome
Filipin
Hyperlipoproteinemia Type II
Oxidative stress
Fibroblasts
Bilirubin
Type B Niemann-Pick Disease
Type C Niemann-Pick Disease
cholestane-3,5,6-triol
7-ketocholesterol
Oxysterols
Oxidative Stress
Liver
Serum

Keywords

  • Acid lipase deficiency
  • Congenital familial hypercholesterolemia
  • Niemann-Pick type B disease
  • Niemann-Pick type C disease
  • Oxysterols
  • Smith-Lemli-Opitz syndrome

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

@article{caeeda44624c44b19391e7f1825f9b8d,
title = "Evaluation of plasma cholestane-3 β,5 α,6 β -triol and 7-ketocholesterol in inherited disorders related to cholesterol metabolism",
abstract = "Oxysterols are intermediates of cholesterol metabolism and are generated from cholesterol via either enzymatic or nonenzymatic pathways under oxidative stress conditions. Cholestan-3β, 5α, 6β-triol (c-triol) and 7-ketocholesterol (7-KC) have been proposed as new biomarkers for the diagnosis of Niemann-Pick type C (NP-C) disease, representing an alternative tool to the invasive and time-consuming method of fibroblast filipin test. To test the efficacy of plasma oxysterol determination for the diagnosis of NP-C, we systematically screened oxysterol levels in patients affected by different inherited disorders related with cholesterol metabolism, which included Niemann-Pick type B (NP-B) disease, lysosomal acid lipase (LAL) deficiency, Smith-Lemli-Opitz syndrome (SLOS), congenital familial hypercholesterolemia (FH), and sitosterolemia (SITO). As expected, NP-C patients showed significant increase of both C-triol and 7-KC. Strong increase of both oxysterols was observed in NP-B and less pronounced in LAL deficiency. In SLOS, only 7-KC was markedly increased, whereas in both FH and in SITO, oxysterol concentrations were normal. Interestingly, in NP-C alone, we observed that plasma oxysterols correlate negatively with patient's age and positively with serum total bilirubin, suggesting the potential relationship between oxysterol levels and hepatic disease status. Our results indicate that oxysterols are reliable and sensitive biomarkers of NP-C.-Boenzi, S., F. Deodato, R. Taurisano, B. M. Goffredo, C. Rizzo, and C. Dionisi-Vici. Evaluation of plasma cholestane-3β, 5α, 6β-triol and 7-ketocholesterol in inherited disorders related to cholesterol metabolism.",
keywords = "Acid lipase deficiency, Congenital familial hypercholesterolemia, Niemann-Pick type B disease, Niemann-Pick type C disease, Oxysterols, Smith-Lemli-Opitz syndrome",
author = "Sara Boenzi and Federica Deodato and Roberta Taurisano and Goffredo, {Bianca Maria} and Cristiano Rizzo and Carlo Dionisi-Vici",
year = "2016",
month = "3",
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doi = "10.1194/jlr.M061978",
language = "English",
volume = "57",
pages = "361--367",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
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T1 - Evaluation of plasma cholestane-3 β,5 α,6 β -triol and 7-ketocholesterol in inherited disorders related to cholesterol metabolism

AU - Boenzi, Sara

AU - Deodato, Federica

AU - Taurisano, Roberta

AU - Goffredo, Bianca Maria

AU - Rizzo, Cristiano

AU - Dionisi-Vici, Carlo

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Oxysterols are intermediates of cholesterol metabolism and are generated from cholesterol via either enzymatic or nonenzymatic pathways under oxidative stress conditions. Cholestan-3β, 5α, 6β-triol (c-triol) and 7-ketocholesterol (7-KC) have been proposed as new biomarkers for the diagnosis of Niemann-Pick type C (NP-C) disease, representing an alternative tool to the invasive and time-consuming method of fibroblast filipin test. To test the efficacy of plasma oxysterol determination for the diagnosis of NP-C, we systematically screened oxysterol levels in patients affected by different inherited disorders related with cholesterol metabolism, which included Niemann-Pick type B (NP-B) disease, lysosomal acid lipase (LAL) deficiency, Smith-Lemli-Opitz syndrome (SLOS), congenital familial hypercholesterolemia (FH), and sitosterolemia (SITO). As expected, NP-C patients showed significant increase of both C-triol and 7-KC. Strong increase of both oxysterols was observed in NP-B and less pronounced in LAL deficiency. In SLOS, only 7-KC was markedly increased, whereas in both FH and in SITO, oxysterol concentrations were normal. Interestingly, in NP-C alone, we observed that plasma oxysterols correlate negatively with patient's age and positively with serum total bilirubin, suggesting the potential relationship between oxysterol levels and hepatic disease status. Our results indicate that oxysterols are reliable and sensitive biomarkers of NP-C.-Boenzi, S., F. Deodato, R. Taurisano, B. M. Goffredo, C. Rizzo, and C. Dionisi-Vici. Evaluation of plasma cholestane-3β, 5α, 6β-triol and 7-ketocholesterol in inherited disorders related to cholesterol metabolism.

AB - Oxysterols are intermediates of cholesterol metabolism and are generated from cholesterol via either enzymatic or nonenzymatic pathways under oxidative stress conditions. Cholestan-3β, 5α, 6β-triol (c-triol) and 7-ketocholesterol (7-KC) have been proposed as new biomarkers for the diagnosis of Niemann-Pick type C (NP-C) disease, representing an alternative tool to the invasive and time-consuming method of fibroblast filipin test. To test the efficacy of plasma oxysterol determination for the diagnosis of NP-C, we systematically screened oxysterol levels in patients affected by different inherited disorders related with cholesterol metabolism, which included Niemann-Pick type B (NP-B) disease, lysosomal acid lipase (LAL) deficiency, Smith-Lemli-Opitz syndrome (SLOS), congenital familial hypercholesterolemia (FH), and sitosterolemia (SITO). As expected, NP-C patients showed significant increase of both C-triol and 7-KC. Strong increase of both oxysterols was observed in NP-B and less pronounced in LAL deficiency. In SLOS, only 7-KC was markedly increased, whereas in both FH and in SITO, oxysterol concentrations were normal. Interestingly, in NP-C alone, we observed that plasma oxysterols correlate negatively with patient's age and positively with serum total bilirubin, suggesting the potential relationship between oxysterol levels and hepatic disease status. Our results indicate that oxysterols are reliable and sensitive biomarkers of NP-C.-Boenzi, S., F. Deodato, R. Taurisano, B. M. Goffredo, C. Rizzo, and C. Dionisi-Vici. Evaluation of plasma cholestane-3β, 5α, 6β-triol and 7-ketocholesterol in inherited disorders related to cholesterol metabolism.

KW - Acid lipase deficiency

KW - Congenital familial hypercholesterolemia

KW - Niemann-Pick type B disease

KW - Niemann-Pick type C disease

KW - Oxysterols

KW - Smith-Lemli-Opitz syndrome

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