Single nucleotide polymorphism of Methyl-CpG-binding protein 2 gene associates with juvenile idiopathic arthritis

Abstract

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.

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