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OBJECTIVE: To establish linkage and replicate the association of macrophage migration inhibitory factor (MIF) with juvenile idiopathic arthritis (JIA). METHODS: Three hundred twenty-one Caucasian simplex families from the UK were genotyped for polymorphisms of MIF using SNaPshot ddNTP primer extension, or by a fluorescently labeled primer method, and capillary gel electrophoresis. The functional significance of the promoter polymorphisms was studied using luciferase-based reporter gene assays in human T lymphoblast and epithelial cell lines. RESULTS: MIF was linked and associated with JIA (P = 0.0016). Specifically, a 2-point promoter haplotype, CATT(7)-MIF-173*C, was found to be transmitted in excess (38 transmitted: 21 not transmitted) in the JIA patients. Conditional extended transmission disequilibrium test and pairwise extended transmission disequilibrium test predicted functional interaction between the 2 polymorphic positions. The interaction of the CATT repeat with MIF-173*G/C was found to be specific to the cell type. CONCLUSION: Replication of an association and linkage of MIF with JIA has been established. Functional interaction between the polymorphic positions on the linked haplotype has also been shown. The molecular mechanism of this interaction is currently being investigated.

Original publication

DOI

10.1002/art.20178

Type

Journal article

Journal

Arthritis Rheum

Publication Date

05/2004

Volume

50

Pages

1604 - 1610

Keywords

Arthritis, Juvenile, C-Reactive Protein, Cell Line, Genes, Reporter, Genetic Linkage, Haplotypes, Humans, Macrophage Migration-Inhibitory Factors, Polymorphism, Genetic, Promoter Regions, Genetic, Respiratory Mucosa, T-Lymphocytes, Transfection