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




This multi-center, prospective, longitudinal observational study aims at determining whether the adverse effects of lipoprotein cholesterol (LDL-C), and total cholesterol (TC) in CIS progression are associated with decreased levels of vitamin D. Furthermore it investigates how to better define the mechanisms mediating the inter-dependence between vitamin D and cholesterol pathways by systematically assessing the roles of lipoproteins, apolipoproteins, cholesteryl esters fatty acid composition, and genetic factors.

The study enrolled CIS patients within four months of the clinical event with the following characteristics: 18–55 years old, Expanded Disability Status Scale (EDSS) 3.5, presence of oligoclonal bands in CSF obtained at the screening visit prior to steroid treatment and presence of T2-hyperintense lesions on diagnostic MRI. Clinical and MRI outcomes (including time to clinically-definite MS, disability progression measures and volumetric MRI scans) were obtained longitudinally. MRI assessments were obtained at baseline 6, 12, and 24 months. Clinical assessments were performed using the EDSS. Demographic and clinical information, statin and thyroid medication use history, height and weight, and non-fasting lipid profile laboratory values: HDL-C, LDL-C, triglycerides, TC were obtained. None of the patients were on statins. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) was used to measure the vitamin D metabolites: 25 hydroxy vitamin D3 (25(OH)D3), 1,25 dihydroxy vitamin D3 (1,25(OH)2 D3) and 24,25 dihydroxy vitamin D3 (24,25(OH)2 D3). A broad range of cholesterol pathway biomarkers was associated with 25(OH)D3 levels.

The authors found higher HDL-C and LDL- C levels were associated with higher 25(OH)D3 and 1,25-(OH)2 D3 levels. This finding precludes the possibility that decreases in vitamin D mediate the adverse effects of increased cholesterol biomarkers on MRI outcomes in CIS. They also found that genetic variations in 7-dehydrocholesterol reductase (DHC7R rs1790349), endothelial lipase (LIPG rs4939883) and proprotein convertase subtilisin/kexin type 9 (PCSK9 rs11206510) were associated with 25(OH)D3 levels. This suggests that cholesterol supply could be an important determinant of vitamin D levels in vivo. However, these findings should be confirmed in larger studies.

Authors: Browne RW, Weinstock-Guttman B
Source: J Steroid Biochem Mol Biol. 2014 Jun 17. pii: S0960-0760(14)00121-6. doi: 10.1016/j.jsbmb.2014.06.007. [Epub ahead of print]
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