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 language | English |
|---|---|
| Pages (from-to) | 424-433 |
| Number of pages | 10 |
| Journal | Journal of Steroid Biochemistry and Molecular Biology |
| Volume | 143 |
| DOIs | |
| Publication status | Published - 2014 |
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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 journal › Article
}
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 -