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Expression of CYP24A1 and other multiple sclerosis risk genes in peripheral blood indicates response to vitamin D in homeostatic and inflammatory conditions
Genes and Immunity ( IF 5.0 ) Pub Date : 2021-06-23 , DOI: 10.1038/s41435-021-00144-6
Samantha P L Law 1 , Prudence N Gatt 1 , Stephen D Schibeci 1 , Fiona C McKay 1 , Steve Vucic 1 , Prue Hart 2 , Scott N Byrne 1 , David Brown 1 , Graeme J Stewart 1 , Christopher Liddle 1 , Grant P Parnell 1 , David R Booth 1
Affiliation  

Although genetic and epidemiological evidence indicates vitamin D insufficiency contributes to multiple sclerosis (MS), and serum levels of vitamin D increase on treatment with cholecalciferol, recent metanalyses indicate that this vitamin D form does not ameliorate disease. Genetic variation in genes regulating vitamin D, and regulated by vitamin D, affect MS risk. We evaluated if the expression of vitamin D responsive MS risk genes could be used to assess vitamin D response in immune cells. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls and people with MS treated with dimethyl fumarate. We assayed changes in expression of vitamin D responsive MS risk (VDRMS) genes in response to treatment with 25 hydroxy vitamin D in the presence or absence of inflammatory stimuli. Expression of CYP24A1 and other VDRMS genes was significantly altered in PBMCs treated with vitamin D in the homeostatic and inflammatory models. Gene expression in MS samples had similar responses to controls, but lower initial expression of the risk genes. Vitamin D treatment abrogated these differences. Expression of CYP24A1 and other MS risk genes in blood immune cells indicate vitamin D response and could enable assessment of immunological response to vitamin D in clinical trials and on therapy.



中文翻译:

CYP24A1 和其他多发性硬化症风险基因在外周血中的表达表明在稳态和炎症条件下对维生素 D 的反应

尽管遗传学和流行病学证据表明维生素 D 不足会导致多发性硬化症 (MS),并且胆钙化醇治疗后血清维生素 D 水平会升高,但最近的荟萃分析表明这种维生素 D 形式不会改善疾病。调节维生素 D 和受维生素 D 调节的基因的遗传变异会影响 MS 风险。我们评估了维生素 D 反应性 MS 风险基因的表达是否可用于评估免疫细胞中的维生素 D 反应。外周血单核细胞 (PBMC) 分离自健康对照和接受富马酸二甲酯治疗的 MS 患者。我们检测了在存在或不存在炎症刺激的情况下,维生素 D 反应性 MS 风险 (VDRMS) 基因表达对 25 羟基维生素 D 治疗的反应变化。在体内平衡和炎症模型中,用维生素 D 处理的 PBMC 中 CYP24A1 和其他 VDRMS 基因的表达发生显着改变。MS 样本中的基因表达与对照有相似的反应,但风险基因的初始表达较低。维生素 D 治疗消除了这些差异。CYP24A1 和其他 MS 风险基因在血液免疫细胞中的表达表明维生素 D 反应,并且可以在临床试验和治疗中评估对维生素 D 的免疫反应。

更新日期:2021-06-23
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