A novel 5′‐flanking region polymorphism of macrophage migration inhibitory factor is associated with systemic‐onset juvenile idiopathic arthritis

Abstract

To determine if polymorphisms of the macrophage migration inhibitory factor (MIF) gene are associated with systemic-onset juvenile idiopathic arthritis (JIA). Denaturing high-performance liquid chromatography was used to screen for the MIF gene in 32 healthy Caucasian subjects. One hundred seventeen UK Caucasian patients with systemic-onset JIA and 172 unrelated healthy UK Caucasian controls were genotyped for a single-nucleotide polymorphism (SNP) identified in the 5'-flanking region of the gene, using polymerase chain reaction-restriction fragment length analysis. A G-to-C transition was identified at position -173 of the MIF gene. The presence of a C at -173 creates an activator protein 4 transcription factor binding site. Allele and genotype frequencies differed significantly between the patients and controls for the MIF-173 polymorphism. Individuals possessing a MIF-173*C allele have an increased risk of systemic-onset JIA (36.8% versus 20.3%) (odds ratio 2.3, 95% confidence interval 1.34-3.86; P = 0.0005). This is the first report of a SNP in the MIF gene. This polymorphism is associated with systemic-onset JIA.