Abstract
BackgroundJohne's disease is a chronic inflammatory bowel disease (IBD) of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). Since this pathogen has been implicated in the pathogenesis of human IBDs, the goal of this study was to assess whether single nucleotide polymorphism (SNPs) in several well-known candidate genes for human IBD are associated with susceptibility to MAP infection in dairy cattle.MethodsThe bovine candidate genes, interleukin-10 (IL10), IL10 receptor alpha/beta (IL10RA/B), transforming growth factor beta 1 (TGFB1), TGFB receptor class I/II (TGFBR1/2), and natural resistance-associated macrophage protein 1 (SLC11A1) were sequenced for SNP discovery using pooled DNA samples, and the identified SNPs were genotyped in a case-control association study comprised of 242 MAP negative and 204 MAP positive Holstein dairy cattle. Logistic regression was used to determine the association of SNPs and reconstructed haplotypes with MAP infection status.ResultsA total of 13 SNPs were identified. Four SNPs in IL10RA (984G > A, 1098C > T, 1269T > C, and 1302A > G) were tightly linked, and showed a strong additive and dominance relationship with MAP infection status. Haplotypes AGC and AAT, containing the SNPs IL10RA 633C > A, 984G > A and 1185C > T, were associated with an elevated and reduced likelihood of positive diagnosis by serum ELISA, respectively.ConclusionsSNPs in IL10RA are associated with MAP infection status in dairy cattle. The functional significance of these SNPs warrants further investigation.
Highlights
Johne's disease is a chronic inflammatory bowel disease (IBD) of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP)
Model selection based on Akaike's information criterion (AIC) subsequently determined that IL10RA 1185C > T was the most appropriate single nucleotide polymorphism (SNPs) to remove from the final multiple regression model
The present study found no association between variants in the bovine IL10 gene and MAP infection, it did provide evidence that variants in the IL10RA gene, which encodes the ligand-binding subunit of the IL10R and is a major determinant of IL10 responsiveness [34,35], may contribute to susceptibility to MAP infection
Summary
Johne's disease is a chronic inflammatory bowel disease (IBD) of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). Since MAP is a slow-growing intracellular pathogen, infected cattle typically remain asymptomatic for 2 to 10 years making it difficult to control Johne's disease in dairy herds [1]. During this asymptomatic period, the pathogen can be horizontally transmitted to other herd members via contaminated feces, and vertically. The presence of MAP in milk poses a potential zoonotic risk to humans [2] This may be relevant for individuals that are genetically predisposed to IBD, since MAP has been implicated as one of several potential pathogens associated with Crohn's disease [3]. Clinical studies have shown that anti-mycobacterial treatment of some patients with Crohn's disease can lead to pathological remission [5]
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