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

Objective. To determine if polymorphisms of the macrophage migration inhibi tory factor (MIF) gene are associated with systemic-onset juvenile idiopath ic arthritis (JIA). Methods. Denaturing high-performance liquid chromatography was used to scre en 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 (SN P) identified in the 5'-flanking region of the gene, using polymerase chain reaction-restriction fragment length analysis. Results. A G-to-C transition was identified at position -173 of the MIF gen e. The presence of a C at -173 creates an activator protein 4 transcription factor binding site. Allele and genotype frequencies differed significantl y between the patients and controls for the MIF-173 polymorphism. Individua ls possessing a MIF-173*C allele have an increased risk of systemic-onset J IA (36.8% versus 20.3%) (odds ratio 2.3, 95% confidence interval 1.34-3.86; P = 0.0005). Conclusion. This is the first report of a SNP in the MIF gene. This polymor phism is associated with systemic-onset JIA.