RESUMO
Control of major mycobacterial diseases affecting livestock is a challenging issue that requires different approaches. The use of genetic markers for improving resistance to Mycobacterium avium subsp. paratuberculosis infection in cattle has been explored as a promising population strategy We performed paratuberculosis epidemiopathogenic phenotypic and genotypic characterization involving 24 SNPs in six candidate genes (NOD2, CD209, SLC11A1, SP110, TLR2 and TLR4) on 502 slaughtered Friesian cows. In the current study, we investigate whether recently proposed paratuberculosis (PTB) epidemiopathogenic (EP) forms (apparently free-AF, latent-LAT and patent-PAT) could be associated with some combination of these 24 SNPs. Best EP form grouping was obtained using a combination of 5 SNPs in four genes (CD209: rs210748127; SLC11A1: rs110090506; SP110: rs136859213 and rs110480812; and TLR2: rs41830058). These groups were defined according to the level of infection progression risk to patent epidemiopathogenic forms and showed the following distributions: LOWIN (low) with 39 (8%) cases (94.9% AF/5.1% LAT/0% PAT); LATIN (low) with 17 (3%) cases (5.9% AF/94.1% LAT/0% PAT); AVERIN (average) with 413 (82%) cases (52.1% AF/38.5% LAT/9.4% PAT) and PATIN (patent) with 33 (7%) cases (36.4% AF/24.2% LAT/39.4% PAT). Age of slaughter was significantly higher for LATIN (88.3 months) compared to AVERIN (65.3 months; p = 0.0007) and PATIN (59.1 months; p = 0.0004), and for LOWIN (73.9 months) compared to PATIN (p = 0.0233), and nearly significant compared to AVERIN (p = 0.0572) These results suggest that some selected genetic polymorphisms have a potential use as markers of PTB EP forms and thus add a new tool for the control of this widespread infection.
RESUMO
A genetic susceptibility to Mycobacterium avium subsp. paratuberculosis (MAP) infections in ruminants has been longtime suspected to exist. Recently, natural infections in cattle have been reclassified into latent and patent forms based on histopathological findings and their associations with immunological and microbiological variables. This study aims to explore whether these newly defined phenotypes are associated with twenty-four single-nucleotide polymorphisms (SNPs) in six bovine candidate genes: nucleotide-binding oligomerization domain 2 (NOD2), solute carrier family 11 member A1 (SLC11A1), nuclear body protein SP110 (SP110), toll-like receptors (TLRs) 2 and 4, and CD209 (also known as DC-SIGN, dendritic cell-specific ICAM3-grabbing nonintegrin). SNPs were genotyped for 772 Holstein-Friesian animals (52.6% apparently free; 38.1% latent; 9.3% patent) by TaqMan OpenArray technology. Genotypic-phenotypic associations were assessed by logistic regression analysis adjusted for age at slaughter, under five models (codominant, dominant, recessive, overdominant, and log-additive), and corrected for multiple testing. The rs208222804 C allele (CD209 gene) was found to be associated with latent paratuberculosis (log-additive model: P < 0.0034 after permutation procedure; OR = 0.64, 95% CI = 0.48-0.86). No significant association was detected between any SNP and the patent phenotype. Consequently, CD209 gene may play a key role in the pathogenesis of bovine paratuberculosis.