Cheng Yafen, Huang ChenShen, Tsai Hsiang-Jung
School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan.
J Vet Med Sci. 2016 Jun 1;78(5):727-32. doi: 10.1292/jvms.15-0506. Epub 2016 Feb 13.
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-α 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-α gene on bovine tuberculosis (bTB) susceptibility. We genotyped the TNF-α gene in 74 bTB-infected Holstein cows and 90 healthy control animals. The influence in the exon 3 region of TNF-α polymorphisms on bTB susceptibility was subsequently investigated by association analysis. Our finding demonstrated that the g.27534932A>C polymorphism of the TNF-α 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-α 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-α 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-α-mediated bTB susceptibility.
许多研究表明，牛和人类对牛分枝杆菌（结核分枝杆菌病的病原体）感染的抵抗力存在显著的基因变异。TNF-α可促进炎症反应，并在应对分枝杆菌感染时诱导细胞凋亡。本研究的目的是调查TNF-α基因单核苷酸多态性对牛结核病（bTB）易感性的影响。我们对74头感染bTB的荷斯坦奶牛和90头健康对照动物的TNF-α基因进行了基因分型。随后通过关联分析研究了TNF-α基因外显子3区域多态性对bTB易感性的影响。我们的研究结果表明TNF-α基因的g.27534932A>C多态性与荷斯坦牛的bTB有关。与CC基因型相比，具有g.27534932A>C基因型的牛的易感性高4.11倍（95%CI，1.27 - 13.36；P = 0.02）。g.27534932A>C多态性位于TNF-α基因的外显子3中，其功能结果是错义突变。推导的蛋白质产物氨基酸序列显示第159位的精氨酸转化为丝氨酸，这可能会影响蛋白质合成的起始并破坏保护动物免受分枝杆菌感染的正常TNF-α功能。观察到A等位基因作为bTB易感性的危险因素存在显著关联（OR，3.84；95%CI，1.21 - 12.17；P = 0.02）。总之，这是第一份表明g.27534932A>C多态性可能导致TNF-α介导的bTB易感性的报告。
