title: Serum lipoprotein composition and vitamin D metabolite levels in clinically isolated syndromes: Results from a multi-center study.
abstract: BACKGROUND
  High serum cholesterol is adversely associated with clinical and imaging disease progression outcomes in multiple sclerosis (MS) and in clinically isolated syndrome (CIS), the earliest stage of MS. Low vitamin D levels are associated with an increased risk of disease progression.
  
  
  OBJECTIVE
  To investigate the mechanisms mediating the adverse effects of cholesterol in CIS and to determine the role of the nexus between the vitamin D3 (D3) and cholesterol pathways.
  
  
  METHODS
  Multi-center, prospective, longitudinal prospective study.
  
  
  METHODS
  University hospital multiple sclerosis centers.
  
  
  METHODS
  Serum samples were obtained prior to any treatment from study subjects.
  
  
  METHODS
  Serum obtained prior to any treatment from 172 CIS patients enrolled in a multi-center, prospective, longitudinal study (119 females: 53 males, age: 28.1 ± SD 8.1 years) were analyzed for high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (ApoAI), ApoAII, ApoB, ApoE, and lipoprotein-a. Levels of 25-hydroxy vitamin D3 (25(OH)D3), 1,25-dihydroxy D3, and 24,25-dihydroxy D3 were measured using liquid chromatography-mass spectrometry.
  
  
  RESULTS
  Greater levels of HDL-C biomarkers (e.g., HDL-C itself, ApoAI, ApoAII and paroxonase arylesterase activity) and LDL-C biomarkers (e.g., LDL-C itself, Apo B) were associated with greater 25(OH)D3. The effects of HDL-C biomarkers were stronger than those of LDL-C. Free cholesterol and cholesteryl ester levels were positively associated with higher 25(OH)D3 levels. Cholesterol palmitate was particularly potent. The nexus between the D3 and cholesterol pathways was proximal to, or in linkage disequilibrium with, 7-dehydrocholesterol reductase DHCR7 rs1790349, endothelial lipase LIPG rs4939883 and proprotein convertase subtilisin/kexin type 9 PCSK9 rs11206510.
  
  
  CONCLUSIONS
  The associations between cholesterol biomarkers and vitamin D metabolite levels in CIS are consistent with the biochemical inter-dependence between the two pathways. Cholesterol biomarkers should be considered for inclusion as covariates when assessing vitamin D levels in CIS.
authors.affiliation: Department of Biotechnical and Clinical Laboratory Sciences, State University of New York, Buffalo, NY, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Browne
authors.affiliation: Department of Neurology, State University of New York, Buffalo, NY, USA.
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.affiliation: Department of Neurology, State University of New York, Buffalo, NY, USA; Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Zivadinov
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Horakova
authors.affiliation: Department of Biotechnical and Clinical Laboratory Sciences, State University of New York, Buffalo, NY, USA.
authors.forename: Mary Lou
authors.initials: ML
authors.lastname: Bodziak
authors.affiliation: Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Tamaño-Blanco
authors.affiliation: Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA.
authors.forename: Darlene
authors.initials: D
authors.lastname: Badgett
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.
authors.forename: Michaela
authors.initials: M
authors.lastname: Tyblova
authors.affiliation: Department of Radiology, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.
authors.forename: Manuela
authors.initials: M
authors.lastname: Vaneckova
authors.affiliation: Department of Radiology, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Seidl
authors.affiliation: Department of Radiology, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Krasensky
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA; IRCCS, S. Maria Nascente, Don Gnocchi Foundation, Milan, Italy.
authors.forename: Niels
authors.initials: N
authors.lastname: Bergsland
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA.
authors.forename: Deepa P
authors.initials: DP
authors.lastname: Ramasamy
authors.affiliation: Buffalo Neuroimaging Analysis Center, Department of Neurology, State University of New York, Buffalo, NY, USA.
authors.forename: Jesper
authors.initials: J
authors.lastname: Hagemeier
authors.affiliation: Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.affiliation: Department of Neurology, State University of New York, Buffalo, NY, USA; Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, USA. Electronic address: Murali@Buffalo.Edu.
authors.forename: Murali
authors.initials: M
authors.lastname: Ramanathan
mesh_terms: D000328:Adult; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D013577:Syndrome; D014807:Vitamin D / Q000378:metabolism*; D014815:Vitamins / Q000378:metabolism*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014815:Vitamins; D014807:Vitamin D; D002784:Cholesterol
keywords: Cholesterol; Clinically isolated syndromes; Environmental factor; Interactions; Lipid; Multiple sclerosis; Vitamin D