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 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).


CONCLUSIONS
This is the first report of a SNP in the MIF gene. This polymorphism is associated with systemic-onset JIA.
Donn
R P
RP
Epidemiology Unit, Arthritis Research Campaign, Manchester, UK.
Shelley
E
E
Ollier
W E
WE
Thomson
W
W
D020121:5' Untranslated Regions; D001171:Arthritis, Juvenile / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
D020121:5' Untranslated Regions; D008263:Macrophage Migration-Inhibitory Factors