Karaky Mohamad, Alcina Antonio, Fedetz María, Barrionuevo Cristina, Potenciano Victor, Delgado Concepción, Izquierdo Guillermo, Matesanz Fuencisla
Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina "López Neyra" (IPBLN-CSIC), Granada, Spain.
Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina "López Neyra" (IPBLN-CSIC), Granada, Spain
Mult Scler. 2016 Jul;22(8):999-1006. doi: 10.1177/1352458515610208. Epub 2015 Oct 14.
Vitamin D deficit is considered an important risk factor for many inflammatory and autoimmune diseases.
To investigate the influence of the multiple sclerosis (MS)-associated regulatory variant rs10877013 on the expression of genes involved in vitamin D activation (CYP27B1), vitamin D receptor (VDR), and vitamin D degradation (CYP24A1) under inflammatory environment or vitamin D.
We used lipopolysaccharide and interferon-gamma (LPS+IFNγ) activated monocytes from 119 individuals and vitamin D-stimulated lymphoblastoid cell lines (LCLs, n = 109) of 1000 genomes to quantify the mRNA expression of vitamin D genes by quantitative reverse transcription polymerase chain reaction (RT-qPCR).
We found that CYP27B1 mRNA expression level was associated with the rs10877013 genotypes (p = 5.0E-6) in LPS+IFNγ treated monocytes, but not in vitamin D-stimulated LCLs. Inversely, rs10877013 genotypes were associated with VDR expression in LCLs (p = 6.0E-4) but not in monocytes. Finally, CYP24A1 was highly induced by the active form of vitamin D and its expression correlated with the expression of VDR in LCLs but neither the MS-associated variant in the region (rs2248359) nor any other variant located in 1 Mb around CYP24A1 was associated with its expression.
The MS-associated variant rs10877013 is a genetic determinant that affects the functioning of the vitamin D system linking environmental and genetic factors.
维生素D缺乏被认为是许多炎症性和自身免疫性疾病的重要危险因素。
研究与多发性硬化症（MS）相关的调控变异rs10877013在炎症环境或维生素D作用下对参与维生素D激活（CYP27B1）、维生素D受体（VDR）和维生素D降解（CYP24A1）的基因表达的影响。
我们使用脂多糖和干扰素-γ（LPS+IFNγ）激活119名个体的单核细胞以及来自千人基因组计划的100名个体的维生素D刺激的淋巴母细胞系（LCLs，n = 109），通过定量逆转录聚合酶链反应（RT-qPCR）定量维生素D相关基因的mRNA表达。
我们发现，在LPS+IFNγ处理的单核细胞中，CYP27B1 mRNA表达水平与rs10877013基因型相关（p = 5.0E-6），但在维生素D刺激的LCLs中不相关。相反，rs10877013基因型与LCLs中的VDR表达相关（p = 6.0E-4），但在单核细胞中不相关。最后，维生素D的活性形式可高度诱导CYP24A1，其表达与LCLs中VDR的表达相关，但该区域与MS相关的变异（rs2248359）以及位于CYP24A1周围1 Mb内的任何其他变异均与其表达无关。
与MS相关的变异rs10877013是一个遗传决定因素，影响着连接环境和遗传因素的维生素D系统的功能。
