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

Tianchang Lu; Minyi Wang; Nannan Liu; Shuqiong Zhang; Lei Shi; Ling Bao; Feng Luo; Li Shi; Shuyuan Liu; Yufeng Yao

doi:10.2147/PGPM.S404339

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

Pharmgenomics Pers Med. 2023 Apr 13:16:325-336. doi: 10.2147/PGPM.S404339. eCollection 2023.

Authors

Tianchang Lu^#¹, Minyi Wang^#^{1

2}, Nannan Liu¹, Shuqiong Zhang³, Lei Shi¹, Ling Bao³, Feng Luo³, Li Shi¹, Shuyuan Liu¹, Yufeng Yao⁴

Affiliations

¹ Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, 650118, People's Republic of China.
² School of Life Science, Yunnan University, Kunming, 650500, People's Republic of China.
³ Department of Clinical Laboratory, The Third People's Hospital of Kunming, Kunming, 650041, People's Republic of China.
⁴ Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Disease, Kunming, 650118, People's Republic of China.

^# Contributed equally.

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.

Keywords: TAP gene; association; novel allele; polymorphism; tuberculosis.

Grants and funding

This work was supported by Yunnan Fundamental Research Projects (202201AS070059), and Special Funds for high-level health talents of Yunnan Province (L-201615, D-201669, and H-2018014). Author Shuyuan Liu has received research support from Yunnan Fundamental Research Projects, Shuyuan Liu, Yufeng Yao and Li Shi received research support from Special Funds for high-level health talents of Yunnan Province. The funders had no role in the design of the study, data collection and analysis, decision to publish, or preparation of the manuscript.