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
Department of Biotechnical and Clinical Laboratory Sciences, State University of New York, Buffalo, NY, USA.
Department of Neurology, State University of New York, Buffalo, NY, USA.
J Steroid Biochem Mol Biol. 2014 Sep;143:424-33. doi: 10.1016/j.jsbmb.2014.06.007. Epub 2014 Jun 17.
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.
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.
Multi-center, prospective, longitudinal prospective study.
University hospital multiple sclerosis centers.
Serum samples were obtained prior to any treatment from study subjects.
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.
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.
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.
高血清胆固醇与多发性硬化症（MS）以及MS的最早阶段——临床孤立综合征（CIS）的临床和影像学疾病进展结果呈负相关。低维生素D水平与疾病进展风险增加相关。
研究介导胆固醇在CIS中产生不良影响的机制，并确定维生素D3（D3）和胆固醇途径之间联系的作用。
多中心、前瞻性纵向研究。
大学医院多发性硬化症中心。
在研究对象接受任何治疗之前采集血清样本。
对参加多中心、前瞻性纵向研究的172例CIS患者（119名女性，53名男性，年龄：28.1±标准差8.1岁）在接受任何治疗之前采集的血清进行分析，检测高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、载脂蛋白AI（ApoAI）、ApoAII、ApoB、ApoE和脂蛋白-a。使用液相色谱-质谱法测量25-羟基维生素D3（25(OH)D3）、骨化三醇（1,25-二羟基D3）和24,25-二羟基D3的水平。
较高水平的HDL-C生物标志物（如HDL-C本身、ApoAI、ApoAII和对氧磷酶芳基酯酶活性）和LDL-C生物标志物（如LDL-C本身、Apo B）与较高的25(OH)D3相关。HDL-C生物标志物的影响比LDL-C更强。游离胆固醇和胆固醇酯水平与较高的25(OH)D3水平呈正相关。棕榈酸胆固醇酯的作用尤为显著。D3和胆固醇途径之间的联系与7-脱氢胆固醇还原酶DHCR7 rs1790349、内皮脂肪酶LIPG rs4939883和前蛋白转化酶枯草溶菌素/kexin 9型PCSK9 rs11206510接近或处于连锁不平衡状态。
CIS中胆固醇生物标志物与维生素D代谢物水平之间的关联与这两条途径之间的生化相互依存关系一致。在评估CIS中的维生素D水平时，应考虑将胆固醇生物标志物作为协变量纳入。
Zotero 插件