title: A novel protein glycan biomarker and LCAT activity in metabolic syndrome.
abstract: BACKGROUND
  The cholesterol-esterifying enzyme, lecithin:cholesterol acyltransferase (LCAT), is instrumental in high-density lipoprotein (HDL) remodelling. LCAT may also modify oxidative and inflammatory processes, as supported by an inverse relationship with HDL antioxidative functionality and a positive relationship with high-sensitivity C-reactive protein (hsCRP). GlycA is a recently developed proton nuclear magnetic resonance (NMR) spectroscopy-measured biomarker of inflammation whose signal originates from a subset of N-acetylglucosamine residues on the most abundant glycosylated acute-phase proteins. Plasma GlycA correlates positively with hsCRP and may predict cardiovascular disease even independent of hsCRP. Here, we tested the extent to which plasma GlycA is elevated in metabolic syndrome (MetS), and determined its relationship with LCAT activity.
  
  
  METHODS
  Plasma GlycA, hsCRP, serum amyloid A (SAA), tumour necrosis factor-α (TNF-α) and LCAT activity were measured in 58 subjects with MetS (including 46 subjects with type 2 diabetes mellitus (T2DM)) and in 45 nondiabetic subjects without MetS.
  
  
  RESULTS
  Plasma GlycA was higher in MetS coinciding with higher hsCRP and LCAT activity (P < 0.01 for each). In all subjects combined, GlycA was correlated positively with hsCRP, SAA and LCAT activity (P < 0.001 for each), but not with TNF-α. Age- and sex-adjusted multivariable linear regression analysis revealed that GlycA was positively associated with LCAT activity (P = 0.029), independent of the presence of MetS, T2DM, hsCRP and SAA. GlycA was unrelated to diabetes status.
  
  
  CONCLUSIONS
  A pro-inflammatory glycoprotein biomarker, GlycA, is higher in MetS. Higher plasma levels of this glycoprotein biomarker relate to increased LCAT activity in the setting of MetS.
authors.affiliation: Department of Endocrinology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.|Department of Nephrology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Eke G
authors.initials: EG
authors.lastname: Gruppen
authors.affiliation: LabCorp, Raleigh, NC, USA.
authors.forename: Margery A
authors.initials: MA
authors.lastname: Connelly
authors.affiliation: LabCorp, Raleigh, NC, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Otvos
authors.affiliation: Department of Nephrology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Department of Endocrinology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
mesh_terms: D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D005260:Female; D006801:Humans; D016014:Linear Models; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000150:complications; D008875:Middle Aged; D015999:Multivariate Analysis; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood*; D011509:Proteoglycans / Q000097:blood*; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D011509:Proteoglycans; D000685:Serum Amyloid A Protein; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D007862:Phosphatidylcholine-Sterol O-Acyltransferase
keywords: Diabetes mellitus; glycoproteins; high-sensitivity C-reactive; lecithin:cholesterol acyltransferase; metabolic syndrome