Donn RP, ShelleyE, Ollier WER, Thomson W, British Paediatric Rheumatology Study Group
Arthritis and Rheumatism. 2001;44, 8:1782-1785.
OBJECTIVE: To determine if polymorphisms of the macrophage migration inhibitory factor
(MIF) gene are associated with systemic-onset juvenile idiopathic arthritis (JIA).
METHODS: 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.
RESULTS: 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). CONCLUSION: This is the first report
of a SNP in the MIF gene. This polymorphism is associated with systemic-onset JIA