title: Candidate gene polymorphisms (BoIFNG, TLR4, SLC11A1) as risk factors for paratuberculosis infection in cattle.
abstract: Paratuberculosis (Johne's disease) imposes a significant problem to the world dairy and beef industries and today is considered a potential zoonosis. The disease is caused by Mycobacterium avium subsp. paratuberculosis and is characterized by progressive weight loss and profuse diarrhoea. Susceptibility to infection is suspected to have a genetic component, and moderated values for heritability of infection have been reported. Interferon gamma is an inducible cytokine with a crucial role in the innate host response to intracellular bacteria. Toll-like receptors are trans-membrane structures responsible for coordination of innate and adaptive immune responses. The solute carrier family 11 member 1 (SLC11A1, formerly NRAMP1) gene plays an important role in innate immunity, preventing bacterial growth in macrophages during the initial stages of infection. The objective of this candidate gene case-control study was to characterize the distribution of polymorphisms in three candidate genes related to the immune function; interferon gamma (BoIFNG), toll-like receptor 4 (TLR4), and SLC11A1 genes and to test their role as potential risk factors for paratuberculosis infection in cattle. The statistical analysis demonstrated significant differences in allelic frequencies between cases and controls for BoIFNG-SNP(1)2781 and SLC11A1 microsatellites, indicating a significant association between infection and variant alleles. In the analysis of genotypes, a significant association was also found between infection status and BoIFNG-SNP(1)2781 and SLC11A1-275-279-281 microsatellites. However, when variables such as breed and age were included in the multivariate logistic regression analysis, a tendency toward statistical significance for the effect of polymorphisms in the odds of infection was only found for alleles SLC11A1-275 and 279.
authors.affiliation: Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0136, USA.
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Pinedo
authors.forename: Claus D
authors.initials: CD
authors.lastname: Buergelt
authors.forename: G Art
authors.initials: GA
authors.lastname: Donovan
authors.forename: Pedro
authors.initials: P
authors.lastname: Melendez
authors.forename: Laurence
authors.initials: L
authors.lastname: Morel
authors.forename: Rongling
authors.initials: R
authors.lastname: Wu
authors.forename: Taimour Y
authors.initials: TY
authors.lastname: Langaee
authors.forename: D Owen
authors.initials: DO
authors.lastname: Rae
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D002417:Cattle; D002418:Cattle Diseases / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology*; D004247:DNA / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000382:microbiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D007371:Interferon-gamma / Q000235:genetics*; D016927:Mycobacterium avium subsp. paratuberculosis / Q000302:isolation & purification; D010283:Paratuberculosis / Q000453:epidemiology* / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D018401:Sample Size; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D004247:DNA; D007371:Interferon-gamma; D051197:Toll-Like Receptor 4; D000099173:Natural Resistance-associated Macrophage Protein 1