Serum lipoprotein composition and vitamin D metabolite levels in clinically isolated syndromes: Results from a multi-center study

Richard W. Browne, Bianca Weinstock-Guttman, Robert Zivadinov, Dana Horakova, Mary Lou Bodziak, Miriam Tamaño-Blanco, Darlene Badgett, Michaela Tyblova, Manuela Vaneckova, Zdenek Seidl, Jan Krasensky, Niels Bergsland, Deepa P. Ramasamy, Jesper Hagemeier, Jun Qu, Eva Havrdova, Murali Ramanathan

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Context 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. Objectives 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. Design Multi-center, prospective, longitudinal prospective study. Setting University hospital multiple sclerosis centers. Intervention 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.

Original languageEnglish
Pages (from-to)424-433
Number of pages10
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume143
DOIs
Publication statusPublished - 2014

Fingerprint

Metabolites
Vitamin D
Lipoproteins
Biomarkers
Cholesterol
HDL Cholesterol
Serum
Chemical analysis
LDL Cholesterol
Multiple Sclerosis
Cholesterol Esters
Cholecalciferol
Apolipoproteins B
Longitudinal Studies
Disease Progression
Proprotein Convertases
Prospective Studies
Subtilisin
Apolipoproteins
Palmitates

Keywords

  • Cholesterol
  • Clinically isolated syndromes
  • Environmental factor
  • Interactions
  • Lipid
  • Multiple sclerosis
  • Vitamin D

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Cell Biology
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Molecular Medicine

Cite this

Serum lipoprotein composition and vitamin D metabolite levels in clinically isolated syndromes : Results from a multi-center study. / Browne, Richard W.; Weinstock-Guttman, Bianca; Zivadinov, Robert; Horakova, Dana; Bodziak, Mary Lou; Tamaño-Blanco, Miriam; Badgett, Darlene; Tyblova, Michaela; Vaneckova, Manuela; Seidl, Zdenek; Krasensky, Jan; Bergsland, Niels; Ramasamy, Deepa P.; Hagemeier, Jesper; Qu, Jun; Havrdova, Eva; Ramanathan, Murali.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 143, 2014, p. 424-433.

Research output: Contribution to journalArticle

Browne, RW, Weinstock-Guttman, B, Zivadinov, R, Horakova, D, Bodziak, ML, Tamaño-Blanco, M, Badgett, D, Tyblova, M, Vaneckova, M, Seidl, Z, Krasensky, J, Bergsland, N, Ramasamy, DP, Hagemeier, J, Qu, J, Havrdova, E & Ramanathan, M 2014, 'Serum lipoprotein composition and vitamin D metabolite levels in clinically isolated syndromes: Results from a multi-center study', Journal of Steroid Biochemistry and Molecular Biology, vol. 143, pp. 424-433. https://doi.org/10.1016/j.jsbmb.2014.06.007
Browne, Richard W. ; Weinstock-Guttman, Bianca ; Zivadinov, Robert ; Horakova, Dana ; Bodziak, Mary Lou ; Tamaño-Blanco, Miriam ; Badgett, Darlene ; Tyblova, Michaela ; Vaneckova, Manuela ; Seidl, Zdenek ; Krasensky, Jan ; Bergsland, Niels ; Ramasamy, Deepa P. ; Hagemeier, Jesper ; Qu, Jun ; Havrdova, Eva ; Ramanathan, Murali. / Serum lipoprotein composition and vitamin D metabolite levels in clinically isolated syndromes : Results from a multi-center study. In: Journal of Steroid Biochemistry and Molecular Biology. 2014 ; Vol. 143. pp. 424-433.
@article{ba5f9e0cb2a54e26a4a9c3a317bdfe7b,
title = "Serum lipoprotein composition and vitamin D metabolite levels in clinically isolated syndromes: Results from a multi-center study",
abstract = "Context 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. Objectives 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. Design Multi-center, prospective, longitudinal prospective study. Setting University hospital multiple sclerosis centers. Intervention 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.",
keywords = "Cholesterol, Clinically isolated syndromes, Environmental factor, Interactions, Lipid, Multiple sclerosis, Vitamin D",
author = "Browne, {Richard W.} and Bianca Weinstock-Guttman and Robert Zivadinov and Dana Horakova and Bodziak, {Mary Lou} and Miriam Tama{\~n}o-Blanco and Darlene Badgett and Michaela Tyblova and Manuela Vaneckova and Zdenek Seidl and Jan Krasensky and Niels Bergsland and Ramasamy, {Deepa P.} and Jesper Hagemeier and Jun Qu and Eva Havrdova and Murali Ramanathan",
year = "2014",
doi = "10.1016/j.jsbmb.2014.06.007",
language = "English",
volume = "143",
pages = "424--433",
journal = "Journal of Steroid Biochemistry and Molecular Biology",
issn = "0960-0760",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Serum lipoprotein composition and vitamin D metabolite levels in clinically isolated syndromes

T2 - Results from a multi-center study

AU - Browne, Richard W.

AU - Weinstock-Guttman, Bianca

AU - Zivadinov, Robert

AU - Horakova, Dana

AU - Bodziak, Mary Lou

AU - Tamaño-Blanco, Miriam

AU - Badgett, Darlene

AU - Tyblova, Michaela

AU - Vaneckova, Manuela

AU - Seidl, Zdenek

AU - Krasensky, Jan

AU - Bergsland, Niels

AU - Ramasamy, Deepa P.

AU - Hagemeier, Jesper

AU - Qu, Jun

AU - Havrdova, Eva

AU - Ramanathan, Murali

PY - 2014

Y1 - 2014

N2 - Context 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. Objectives 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. Design Multi-center, prospective, longitudinal prospective study. Setting University hospital multiple sclerosis centers. Intervention 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.

AB - Context 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. Objectives 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. Design Multi-center, prospective, longitudinal prospective study. Setting University hospital multiple sclerosis centers. Intervention 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.

KW - Cholesterol

KW - Clinically isolated syndromes

KW - Environmental factor

KW - Interactions

KW - Lipid

KW - Multiple sclerosis

KW - Vitamin D

UR - http://www.scopus.com/inward/record.url?scp=84903292646&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903292646&partnerID=8YFLogxK

U2 - 10.1016/j.jsbmb.2014.06.007

DO - 10.1016/j.jsbmb.2014.06.007

M3 - Article

C2 - 24950029

AN - SCOPUS:84903292646

VL - 143

SP - 424

EP - 433

JO - Journal of Steroid Biochemistry and Molecular Biology

JF - Journal of Steroid Biochemistry and Molecular Biology

SN - 0960-0760

ER -