title: Single nucleotide polymorphisms alter the promoter activity of bovine MIF.
abstract: Macrophage migration inhibitory factor (MIF) is a unique pro-inflammatory cytokine whose chief functions include modulating TLR4 expression, and suppressing the anti-inflammatory effects of glucocorticoids. Not surprisingly, MIF is involved in a number of inflammatory diseases and single nucleotide polymorphisms (SNPs) have been implicated in modulating disease severity. The objective of the present study was to determine if SNPs in 5' region of bovine MIF affects its promoter activity. Three SNPs were identified, -1078A>G, -395A>G, and -400G>C, all of which fall within predicted transcription factor binding regions. Reporter gene assays indicate that the identified SNPs have a significant effect of modulating MIF promoter activity. Finally, gene association analysis suggests a significant relationship of -395A>G with the susceptibility to Mycobacterium avium ssp. paratuberculosis infection, the causative agent of Johne's disease. Given the relationships revealed in the current study, it is clear that the role of MIF in bovine diseases such as Johne's disease merits further investigation.
authors.affiliation: Centre for Genetic Improvement of Livestock, Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, Canada.
authors.forename: C P
authors.initials: CP
authors.lastname: Verschoor
authors.forename: S D
authors.initials: SD
authors.lastname: Pant
authors.forename: Q
authors.initials: Q
authors.lastname: You
authors.forename: F S
authors.initials: FS
authors.lastname: Schenkel
authors.forename: D F
authors.initials: DF
authors.lastname: Kelton
authors.forename: N A
authors.initials: NA
authors.lastname: Karrow
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D007113:Immunity, Innate; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D010283:Paratuberculosis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D014157:Transcription Factors