Ghavidel Afshin Abdi, Shiari Reza, Hassan-Zadeh Vahideh, Farivar Shirin
Faculty of Life Sciences and Biotechnology, Shahid Beheshti University G.C., Tehran, Iran; Student Research Committee, Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Pediatrics, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Mofid Children's Hospital, Pediatrics Infectious Research Center (PIRC), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Allergol Immunopathol (Madr). 2020 Mar-Apr;48(2):182-186. doi: 10.1016/j.aller.2019.08.003. Epub 2019 Dec 31.
Juvenile idiopathic arthritis (JIA) is an autoimmune rheumatic disease, which affects primarily the joints in children under 16 years old. The etiology of JIA is yet unknown but research has shown that JIA is a multifactorial disease implicating several genes and environmental factors. Environmental factors affect immune cells via epigenetic mechanisms. One of the most important epigenetic mechanisms is DNA methylation catalyzed by DNA methyltransferases (DNMTs) and usually associated with gene silencing. In this study, we analyzed the expression of three DNA methyltransferases namely DNMT1, DNMT3a and DNMT3b in peripheral blood mononuclear cells (PBMCs) of patients with JIA and compared it with the expression of these genes in healthy young individuals.
Peripheral blood mononuclear cells of 28 JIA patients and 28 healthy controls were isolated. Total RNA was extracted, cDNA was synthesized and the transcript levels of DNMTs were analyzed by quantitative PCR.
Analysis of DNMT1, DNMT3a and DNMT3b relative gene expression in PBMCs of JIA patients and control individuals shows that the expression of DNMT1 and DNMT3a is reduced significantly by 7 folds and 5.5 folds, respectively, in JIA patients compared to healthy controls. Furthermore, the expression of all three DNMTs were significantly and drastically reduced in young affected males compared to healthy males.
This study shows that the expression of DNMTs is reduced in JIA patients and this reduction is severe in male JIA patients.
青少年特发性关节炎（JIA）是一种自身免疫性风湿疾病，主要影响16岁以下儿童的关节。JIA的病因尚不清楚，但研究表明JIA是一种多因素疾病，涉及多个基因和环境因素。环境因素通过表观遗传机制影响免疫细胞。最重要的表观遗传机制之一是由DNA甲基转移酶（DNMTs）催化的DNA甲基化，通常与基因沉默相关。在本研究中，我们分析了JIA患者外周血单个核细胞（PBMCs）中三种DNA甲基转移酶即DNMT1、DNMT3a和DNMT3b的表达，并将其与健康年轻个体中这些基因的表达进行比较。
分离28例JIA患者和28例健康对照者的外周血单个核细胞。提取总RNA，合成cDNA，并通过定量PCR分析DNMTs的转录水平。
对JIA患者和对照个体PBMCs中DNMT1、DNMT3a和DNMT3b相对基因表达的分析表明，与健康对照相比，JIA患者中DNMT1和DNMT3a的表达分别显著降低了7倍和5.5倍。此外，与健康男性相比，年轻患病男性中所有三种DNMTs的表达均显著且大幅降低。
本研究表明JIA患者中DNMTs的表达降低，且男性JIA患者的这种降低更为严重。
