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Methylation Status of VDR Gene and its Association with Vitamin D Status and VDR Gene Expression in Pediatric Tuberculosis Disease.
Immunological Investigations ( IF 2.9 ) Pub Date : 2020-08-26 , DOI: 10.1080/08820139.2020.1810702
Kathirvel Maruthai 1 , Saranya Sankar 2 , Mahadevan Subramanian 1
Affiliation  

Deficiency in circulatory vitamin D level and vitamin D receptor DNA methylation could be associated with weakened innate immune response and increased susceptibility to tuberculosis (TB) disease in children. Therefore, we aimed to study the effect of vitamin D receptor (VDR) gene methylation on plasma vitamin D level and the expression of the VDR gene in children with active-TB disease. A cross-sectional comparative study was conducted in 43 children with active-TB and 33 healthy control children (HC). The vitamin D level was measured in plasma, while the levels of VDR gene promoter methylation and VDR gene expression were measured in peripheral blood. Children with active-TB showed a significantly lower median vitamin D level than HC [Cases 17.18 ng/mL (IQR, 8.3–18.6 ng/mL); HC 41.34 ng/mL (IQR, 40.2–43.49 ng/mL) (p<0.0001)] and decreased mRNA expression level of VDR gene [Cases 0.51 (IQR, 0.40–0.70); HC 1.06 (IQR, 0.8–1.2) (p<0.0001)] and increased VDR DNA methylation [Cases 75% (IQR, 50–75%); HC 10% (IQR, 10–25%) (p<0.0001)]. The VDR hypermethylation is significantly associated with reduced vitamin D level and decreased expression level of VDR gene. Therefore this inverse association could be involved in the impairment in the VDR mediated cytolytic and antimicrobial effector cell response in pediatric TB disease.



中文翻译:

VDR 基因的甲基化状态及其与维生素 D 状态和 VDR 基因表达在小儿结核病中的关系。

循环维生素 D 水平和维生素 D 受体 DNA 甲基化的缺乏可能与儿童先天免疫反应减弱和对结核病 (TB) 疾病的易感性增加有关。因此,我们旨在研究维生素 D 受体(VDR)基因甲基化对活动性结核病患儿血浆维生素 D 水平和 VDR 基因表达的影响。在 43 名活动性结核病儿童和 33 名健康对照儿童 (HC) 中进行了一项横断面比较研究。维生素 D 水平在血浆中测量,而 VDR 基因启动子甲基化水平和 VDR 基因表达水平在外周血中测量。患有活动性结核病的儿童的维生素 D 水平中位数显着低于 HC [病例数 17.18 ng/mL (IQR, 8.3–18.6 ng/mL);HC 41.34 ng/mL (IQR, 40.2–43.49 ng/mL) (p<0. 0001)] 和 VDR 基因 mRNA 表达水平降低 [病例 0.51 (IQR, 0.40–0.70); HC 1.06 (IQR, 0.8–1.2) (p<0.0001)] 和增加的 VDR DNA 甲基化 [病例 75% (IQR, 50–75%); HC 10% (IQR, 10–25%) (p<0.0001)]。VDR高甲基化与维生素D水平降低和VDR基因表达水平降低显着相关。因此,这种反向关联可能与小儿结核病中 VDR 介导的溶细胞和抗菌效应细胞反应的损害有关。

更新日期:2020-08-27
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