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.
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.
Authors: Antoine Sreih; Rana Ezzeddine; Lin Leng; Avery LaChance; Geraldine Yu; Yuka Mizue; Lakshman Subrahmanyan; Bernardo A Pons-Estel; Anna-Karin Abelson; Iva Gunnarsson; Elisabet Svenungsson; Joshua Cavett; Stuart Glenn; Lin Zhang; Ruth Montgomery; Andras Perl; Jane Salmon; Marta E Alarcón-Riquelme; John B Harley; Richard Bucala Journal: Arthritis Rheum Date: 2011-12
Authors: James D Falvey; Robert W Bentley; Tony R Merriman; Mark B Hampton; Murray L Barclay; Richard B Gearry; Rebecca L Roberts Journal: World J Gastroenterol Date: 2013-10-21 Impact factor: 5.742
Authors: C Herder; N Klopp; J Baumert; M Müller; N Khuseyinova; C Meisinger; S Martin; T Illig; W Koenig; B Thorand Journal: Diabetologia Date: 2007-08-22 Impact factor: 10.122
Authors: Timothy R D J Radstake; Jaap Fransen; Erik J M Toonen; Marieke J H Coenen; Agnes E Eijsbouts; Rachelle Donn; Frank H J van den Hoogen; Piet L C M van Riel Journal: Ann Rheum Dis Date: 2007-04-24 Impact factor: 19.103