title: Macrophage migration inhibitory factor (MIF) gene polymorphism is associated with susceptibility to but not severity of inflammatory polyarthritis.
abstract: The aim of the study was to investigate whether polymorphisms of macrophage migration inhibitory factor (MIF) determine susceptibility to or severity of inflammatory polyarthritis (IP). Genotypes for a single-nucleotide polymorphism (MIF-173*G/C) and a tetranucleotide (CATT)(n) repeat mapping to the promoter region of the MIF gene were compared between UK Caucasian IP cases (n=438) and controls (n=343). Both polymorphisms were also investigated for association with features of disease activity and severity at baseline and by 5 years. The MIF-173*C allele (OR 1.7, 95% CI 1.3-2.4, P=1.8 x 10(-4)) and the CATT(7) allele (OR 1.5, 95% CI 1.0-2.1, P=0.02) were found to be associated with increased susceptibility to IP. Furthermore, presence of the haplotype containing both associated polymorphisms was associated with a three-fold increase risk of developing IP. No association with disease severity or activity either at baseline or by 5 years was detected for either of the promoter polymorphisms studied. In conclusion, MIF is a susceptibility gene for the development of IP. The same alleles previously reported to be associated with susceptibility to juvenile idiopathic arthritis account for the increased risk. The promoter polymorphisms of MIF, investigated in this study, do not influence the severity of disease outcome by 5 years.
authors.affiliation: Arthritis Rheumatism Campaign Epidemiology Research Unit, University of Manchester, Manchester, UK. ABzarton@fsl.ser.man.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Barton
authors.forename: R
authors.initials: R
authors.lastname: Lamb
authors.forename: D
authors.initials: D
authors.lastname: Symmons
authors.forename: A
authors.initials: A
authors.lastname: Silman
authors.forename: W
authors.initials: W
authors.lastname: Thomson
authors.forename: J
authors.initials: J
authors.lastname: Worthington
authors.forename: R
authors.initials: R
authors.lastname: Donn
mesh_terms: D000328:Adult; D000368:Aged; D001168:Arthritis / Q000235:genetics*; D002874:Chromosome Mapping; D004198:Disease Susceptibility; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics* / Q000276:immunology; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D008263:Macrophage Migration-Inhibitory Factors