Vázquez Patricia, Ruiz-Larrañaga Otsanda, Garrido Joseba M, Iriondo Mikel, Manzano Carmen, Agirre Mikel, Estonba Andone, Juste Ramón A
Department of Animal Health, NEIKER-Tecnalia, Berreaga 1, 48160 Derio, Bizkaia, Spain.
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena S/N, 48940 Leioa, Bizkaia, Spain.
Vet Med Int. 2014;2014:321327. doi: 10.1155/2014/321327. Epub 2014 May 20.
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.
长期以来，人们一直怀疑反刍动物对副结核分枝杆菌（MAP）感染存在遗传易感性。最近，根据组织病理学发现及其与免疫和微生物变量的关联，牛的自然感染已被重新分类为潜伏型和显性型。本研究旨在探讨这些新定义的表型是否与六个牛候选基因中的24个单核苷酸多态性（SNP）相关：核苷酸结合寡聚化结构域2（NOD2）、溶质载体家族11成员A1（SLC11A1）、核体蛋白SP110（SP110）、Toll样受体（TLR）2和4，以及CD209（也称为DC-SIGN，树突状细胞特异性ICAM3结合非整合素）。通过TaqMan OpenArray技术对772头荷斯坦-弗里生牛（52.6%明显未感染；38.1%潜伏感染；9.3%显性感染）进行SNP基因分型。在五个模型（共显性、显性、隐性、超显性和对数加性）下，通过对屠宰年龄进行校正的逻辑回归分析评估基因型与表型的关联，并对多重检验进行校正。发现rs208222804 C等位基因（CD209基因）与潜伏性副结核病相关（对数加性模型：置换程序后P < 0.0034；OR = 0.64，95%CI = 0.48 - 0.86）。未检测到任何SNP与显性表型之间存在显著关联。因此，CD209基因可能在牛副结核病的发病机制中起关键作用。
