Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Pediatric Rheumatology Research Group, Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Clin Rheumatol. 2018 Feb;37(2):375-381. doi: 10.1007/s10067-017-3968-z. Epub 2017 Dec 29.
Methyl-CpG-binding protein 2 (MeCP2) is a transcription suppressor or activator, acting through binding to methylated DNA. Numerous investigations have established a role for methylation aberrancies in the pathogenesis of autoimmune disorders. Single nucleotide polymorphisms (SNPs) in MECP2 gene have been implicated with susceptibility to rheumatoid arthritis (RA). Here, the plausible association of MECP2 gene polymorphisms was evaluated with juvenile idiopathic arthritis (JIA) predisposition in Iranian pediatric patients. In this case-control association study, 49 JIA patients and 398 age-, sex-, and ethnicity-matched healthy individuals were included. Genotyping of all samples for MECP2 gene rs1734787, rs1734791, rs1734792, and rs17435 polymorphisms was conducted by real-time allelic discrimination PCR technique. Except the AT genotype of rs17435 SNP, none of the alleles and genotypes of other positions were distributed significantly between JIA cases and controls. AT genotype was less frequent in JIA cases and was found to be protective genotype of JIA proneness (OR = 0.42; CI, 0.19-0.90; P = 0.028). Among the haplotypes, CCAA and TTTT were detected to have significant difference between cases and controls (OR = 1.74; CI, 1.01-2.98; P = 0.042 and OR = 1.82; CI, 1.05-3.13; P = 0.028). All positions were in linkage disequilibrium with each other according to D'. MECP2 gene rs17435 polymorphism was associated with JIA predisposition. Considering the involvement of genetic polymorphisms of MECP2 gene in susceptibility to adult-onset RA, this gene might basically play a role in the initiation of arthritis during early stages of life.
甲基化 CpG 结合蛋白 2（MeCP2）是一种转录抑制物或激活物，通过与甲基化 DNA 结合发挥作用。大量研究已经确定了甲基化异常在自身免疫性疾病发病机制中的作用。MECP2 基因中的单核苷酸多态性（SNP）与类风湿关节炎（RA）易感性有关。在这里，评估了 MECP2 基因多态性与伊朗儿科患者幼年特发性关节炎（JIA）易感性的可能关联。在这项病例对照关联研究中，纳入了 49 名 JIA 患者和 398 名年龄、性别和种族匹配的健康对照者。使用实时等位基因区分 PCR 技术对所有样本的 MECP2 基因 rs1734787、rs1734791、rs1734792 和 rs17435 多态性进行基因分型。除了 rs17435 SNP 的 AT 基因型外，其他位置的等位基因和基因型在 JIA 病例和对照组之间没有显著分布。AT 基因型在 JIA 病例中较少，被发现是 JIA 易感性的保护基因型（OR=0.42；95%CI，0.19-0.90；P=0.028）。在单体型中，CCAA 和 TTTT 在病例和对照组之间有显著差异（OR=1.74；95%CI，1.01-2.98；P=0.042 和 OR=1.82；95%CI，1.05-3.13；P=0.028）。根据 D'，所有位置彼此之间均处于连锁不平衡状态。MECP2 基因 rs17435 多态性与 JIA 易感性相关。考虑到 MECP2 基因遗传多态性与成人发病 RA 的易感性有关，该基因可能在生命早期关节炎的起始阶段发挥作用。
