title: Plasma levels of sphingosine-1-phosphate and apolipoprotein M in patients with monogenic disorders of HDL metabolism.
abstract: BACKGROUND
  Apolipoprotein M (apoM) has been identified as a specific sphingosine-1-phosphate (S1P) binding protein of HDL.
  
  
  OBJECTIVE
  To investigate the in vivo effects of disturbed apoM or HDL metabolism we quantified S1P and apoM in plasmas of wild-type, apoM-knock-out, and apoM transgenic mice as well as 50 patients with seven different monogenic disorders of HDL metabolism and their 51 unaffected relatives.
  
  
  RESULTS
  Compared to wild type mice, S1P plasma levels in apoM knock-out and apoM transgenic mice were decreased by 30% and increased by 270%, respectively. Compared to family controls, S1P and apoM levels in apoB-depleted plasma were significantly decreased by in average 34% and 12%, respectively, in heterozygous carriers of mutations in APOA1, LCAT or ABCA1, and by 70% and 48%, respectively, in carriers of two defective alleles in LCAT or ABCA1. Heterozygous mutations in CETP, SCARB1, LIPC, or LIPG did not significantly affect S1P or apoM concentrations. Albumin-corrected molar S1P-to-apoM ratios varied from 0.12 to 0.8 (median 0.3) and were not affected by any mutation. S1P levels in apoB-depleted plasma correlated significantly with HDL-cholesterol and less so with apoM both if apoA-I plasma concentrations were below the median.
  
  
  CONCLUSIONS
  In the context of previous data, our findings can be explained by the existence of a specific apoM and S1P containing HDL subclass which contains a considerable molar excess of apoM over S1P and is critically determined by apoA-I up to a threshold concentration around the median found in a Caucasian population.
authors.affiliation: Institute of Clinical Chemistry, University and University Hospital Zurich, Switzerland.
authors.forename: Ratna
authors.initials: R
authors.lastname: Karuna
authors.forename: Rebekka
authors.initials: R
authors.lastname: Park
authors.forename: Alaa
authors.initials: A
authors.lastname: Othman
authors.forename: Adriaan G
authors.initials: AG
authors.lastname: Holleboom
authors.forename: Mohammad Mahdi
authors.initials: MM
authors.lastname: Motazacker
authors.forename: Iryna
authors.initials: I
authors.lastname: Sutter
authors.forename: Jan Albert
authors.initials: JA
authors.lastname: Kuivenhoven
authors.forename: Lucia
authors.initials: L
authors.lastname: Rohrer
authors.forename: Hugues
authors.initials: H
authors.lastname: Matile
authors.forename: Thorsten
authors.initials: T
authors.lastname: Hornemann
authors.forename: Markus
authors.initials: M
authors.lastname: Stoffel
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Rentsch
authors.forename: Arnold
authors.initials: A
authors.lastname: von Eckardstein
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood / Q000235:genetics; D001053:Apolipoproteins / Q000097:blood* / Q000235:genetics; D000075243:Apolipoproteins M; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood*; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D016014:Linear Models; D008049:Lipase / Q000235:genetics; D008052:Lipid Metabolism, Inborn Errors / Q000097:blood* / Q000235:genetics; D054834:Lipocalins / Q000097:blood* / Q000235:genetics; D008246:Lysophospholipids / Q000097:blood*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics; D051122:Scavenger Receptors, Class B / Q000235:genetics; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood; D013557:Switzerland
chemical_list: C577836:ABCA1 protein, human; C505693:APOA1 protein, human; C400523:APOM protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D000075243:Apolipoproteins M; D015415:Biomarkers; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; C504173:LIPC protein, human; D054834:Lipocalins; D008246:Lysophospholipids; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; C060506:sphingosine 1-phosphate; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; C410382:LIPG protein, human; D008049:Lipase; D013110:Sphingosine