Relationship of bovine NOS2 gene polymorphisms to the risk of bovine tuberculosis in Holstein cattle

Many studies suggest significant genetic variation in the resistance of cattle and humans to infection with Mycobacterium bovis, the causative agent of zoonotic tuberculosis. The inducible nitric oxide synthase (iNOS which is encoded by the NOS2 gene) plays a key role in the immunological control of a broad spectrum of infectious agents. This study aimed to investigate the influence of genetic variations in the promoter of the NOS2 gene on bovine tuberculosis (bTB) susceptibility. In this study, the NOS2 genes of 74 bTB-infected Holstein cows and 90 healthy controls were genotyped using PCR followed by nucleotide sequencing. Polymorphisms at rs207692718, rs109279434, rs209895548, rs385993919, rs433717754, rs383366213, rs466730386, rs715225976, rs525673647, rs720757654 and g.19958101T>G in the promoter region of the NOS2 gene were detected. The g.19958101T>G SNP produced two different conformation patterns (TT and TG) and the TG genotype was over-represented in the bTB group (20.27%) compared with the control group (2.22%). The TG genotype frequency of the g.19958101T>G variant was significantly higher in bTB cattle than in healthy controls (OR, 11.19; 95% CI, 2.47-50.73; P=0.0002). The G allele of the g.19958101T>G polymorphism was more frequent in bTB group when compared to control group (10.14% versus 1.11%). Furthermore, the G allele was a risk factor for bTB susceptibility (OR, 10.04; 95% CI, 2.26-44.65; P=0.0002). In conclusion, the g.19958101T>G polymorphism of the NOS2 gene may contribute to the susceptibility of Holstein cattle to bTB.