Association of the FTO gene polymorphism with the features of the clinical course of tuberculosis infection

Severe tuberculosis, characterized by high mortality and disability rates, presents a significant challenge in the prevention and treatment of the disease. The pathogenesis of this severe form of tuberculosis remains largely elusive. While numerous studies have established a link between host gene polymorphisms and susceptibility to tuberculosis, there is a paucity of researchon genetic susceptibility specifically related to severe TB. This study delves deeper into the relationship between host gene polymorphisms and severe tuberculosis, and provides functional verification of dual-luciferase reporter genes. The study encompassed Han Chinese tuberculosis patients, aged between 15 and 45 years (both inclusive), who were treated at the West China Hospital, a subsidiary of Sichuan University, from January 2013 to December 2020. A total of 558 severe and 579 mild tuberculosis cases were selected for a case-control analysis. Two Tag SNPs sites within the FTO gene were identified to explore the correlation between gene polymorphism and tuberculosis severity. The identified SNPs loci associated with TB severity in the association analysis. Predicting the function of loci associated with tuberculosis severity and completing dual-luciferase reporter gene functional validation. The correlation analysis revealed that the minor allele G of FTO rs16952730 is associated with a decreased risk of severe tuberculosis (ORa 0.828, 95% CI 0.691–0.993, Pa=0.041). In contrast, the GG genotype was found to be associated with a lower risk of severe tuberculosis compared to the AA genotype (ORa 0.636, 95% CI 0.421–0.961, Pa=0.032). The genetic model analysis also indicated that the additive model was associated with a reduced risk of severe tuberculosis (ORa 0.834, 95% CI 0.698–0.996, Pa=0.045). During the functional validation of the dual luciferase reporter gene, a comparative analysis was conducted between the rs16952730-PGL3-promoter-AA and rs16952730-PGL3-promoter-GG recombinant plasmids. This comparison unveiled a statistically significant variance in the relative luciferase expression activity, evidenced by a P value of 0.00295. The FTO gene rs16952730 may serve as a potential functional locus influencing gene expression, potentially correlating with the severity of tuberculosis. Not applicable.