Relationship of bovine TNF-alpha gene polymorphisms with the risk of bovine tuberculosis in Holstein cattle
2016
Cheng, Y. ((National Taiwan University, Taipei (Taiwan). School of Veterinary Medicine), (Centers for Disease Control, Ministry of Health and Welfare, Taipei (Taiwan))) | Huang, C.S. | Tsai, H.J.
Many studies suggest significant genetic variation in the resistance of cattle and humans to infection with Mycobacterium bovis (M. bovis), the causative agent of zoonotic tuberculosis. TNF-alpha promotes inflammation and induces apoptosis in response to mycobacterial infection. The aim of the present study was to investigate the influence of single nucleotide polymorphisms of the TNF-alpha gene on bovine tuberculosis (bTB) susceptibility. We genotyped the TNF-alpha gene in 74 bTB-infected Holstein cows and 90 healthy control animals. The influence in the exon 3 region of TNF-alpha polymorphisms on bTB susceptibility was subsequently investigated by association analysis. Our finding demonstrated that the g.27534932A>C polymorphism of the TNF-alpha is associated with bTB in Holstein cattle. The susceptibility of cattle with the g.27534932A>C genotype compared with the CC genotype was 4.11-fold (95% CI, 1.27-13.36; P=0.02) higher. The g.27534932A>C polymorphism located in exon 3 of the TNF-alpha gene, and the functional consequence was missense. The deduced amino acid sequence for the protein product revealed an arginine to serine conversion at position 159, which may affect initiation of protein synthesis and disrupt normal TNF-alpha function that protects animals against mycobacterial infection. A significant association was observed with the A allele as a risk factor for bTB susceptibility (OR, 3.84; 95% CI, 1.21-12.17; P=0.02). In conclusion, this is the first report showing that the g.27534932A>C polymorphism may contribute to TNF-alpha-mediated bTB susceptibility.
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