Transporter Associated with Antigen Processing 1 Gene Polymorphisms Increase the Susceptibility to Tuberculosis

Abstract

Purpose Tuberculosis (TB) is known to result from a complex interaction between the host immune response and Mycobacterium infection. The transporter associated with antigen processing (TAP) plays an important role in the processing and presentation pathways for the Mycobacterium tuberculosis ( M. tb ) antigen. To investigate the possible association of the TAP1 and TAP2 genes with TB. Patients and Methods A total of 449 TB patients and 435 control subjects were included in this study, and single nucleotide polymorphisms (SNPs) in the TAP gene, as well as TAP1 and TAP2 alleles, were genotyped. Results TAP gene association analysis of TB diseases showed that rs41551515-T in the TAP1 gene was significantly associated with susceptibility to TB ( P =7.96E-04, OR=4.124, 95% CI: 1.683–10.102), especially pulmonary TB (PTB, P =6.84E-04, OR=4.350, 95% CI: 1.727–10.945), and the combination of rs1057141-T-rs1135216-C in the TAP1 gene significantly increased the risk of TB susceptibility ( P =5.51E-05, OR=10.899, 95% CI: 2.555–46.493). Five novel TAP1 alleles were detected in Yunnan Han people, and the allele frequency of TAP1*unknown_3 (rs41555220-rs41549617-rs1057141-rs1135216-rs1057149-rs41551515: C-A-T-C-C-T) was notably increased in all TB patients, including in the PTB and EPTB subgroups, and was significantly associated with the risk of susceptibility to TB. However, no association between the TAP2 gene and TB was found in this study. Conclusion Host genetic variants of rs41551515-T and the combination rs1057141-T-rs1135216-C, as well as TAP1*unknown_3 may play a critical role in susceptibility to TB disease.

Advancing tuberculosis management: the role of predictive, preventive, and personalized medicine

“…CYP2C8 and CYP2E1 variants were linked to a higher susceptibility to TB, implying the identification of these variants could be critical in defining new therapeutic strategies for chemoprevention. Recently, genetic variants in the cytokine genes ( IFGN , IL-12 , IL14 , TNFB , and IL1RA ) and transporter associated with TAP were associated with the susceptibility to pulmonary TB and genetic variants in LIA4H , P2RX7 , DCSIGN , and SP110 associated with susceptibility to LTBI ( Abhimanyu et al, 2023 ; Lu et al, 2023 ). While these studies make valuable contributions to expanding the understanding of the genetic basis of PTB and EPTB manifestations, further research is warranted with larger sample sizes and diverse populations.…”