A functional promoter haplotype of macrophage migration inhibitory factor is linked and associated with juvenile idiopathic arthritis
Open Access
- 6 May 2004
- journal article
- research article
- Published by Wiley in Arthritis & Rheumatism
- Vol. 50 (5), 1604-1610
- https://doi.org/10.1002/art.20178
Abstract
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, CATT7–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.Keywords
This publication has 31 references indexed in Scilit:
- Macrophage migration inhibitory factor (MIF) gene polymorphism is associated with susceptibility to but not severity of inflammatory polyarthritisGenes & Immunity, 2003
- Macrophage migration inhibitory factor, MIF alleles, and the genetics of inflammatory disorders: Incorporating disease outcome into the definition of phenotypeArthritis & Rheumatism, 2003
- Macrophage migration inhibitory factor: An emerging therapeutic target in rheumatoid arthritisArthritis & Rheumatism, 2003
- Control of fibroblast‐like synoviocyte proliferation by macrophage migration inhibitory factorArthritis & Rheumatism, 2003
- Macrophage migration inhibitory factor in patients with juvenile idiopathic arthritisArthritis & Rheumatism, 2002
- Adaptation of the extended transmission/disequilibrium test to distinguish disease associations of multiple loci: the Conditional Extended Transmission/Disequilibrium TestAnnals of Human Genetics, 2000
- Conditional ETDT analysis of the Human Leukocyte Antigen region in type 1 diabetesAnnals of Human Genetics, 2000
- Regulation of macrophage migration inhibitory factor by endogenous glucocorticoids in rat adjuvant-induced arthritisArthritis & Rheumatism, 2000
- Tumour Necrosis Factor α Causes Retention of Activated Glucocorticoid Receptor within the Cytoplasm of A549 CellsBiochemical and Biophysical Research Communications, 1996
- An extended transmission/disequilibrium test (TDT) for multi‐allele marker lociAnnals of Human Genetics, 1995