https://orcid.org/0000-0003-4508-1409
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.
Data Sharing Statement
All the genotyping data of SNPs in TAP1 and TAP2 gene in this study have been deposited in the Figshare database named “Genotypes of SNPs in TAP gene of TB patients and controls” (DOI: https://figshare.com/s/a36d0cda19bc08f17f5e).
Ethics Approval and Informed Consent
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board and Biosecurity Committee of the Third People’s Hospital of Kunming (Kunming, China) (approval number is 2018030720, Date March 07, 2018). And Informed consent was obtained from all individual participants included in the study.
Acknowledgments
We thank all participants for their cooperation. This work was supported by grants from the Yunnan Fundamental Research Projects (202201AS070059), and Special Funds for high-level health talents of Yunnan Province (L-201615, D-201669, and H-2018014). The funders had no role in the design of the study, data collection and analysis, decision to publish, or preparation of the manuscript. Sample collection was also done by the Third People's Hospital of Kunming (Kunming, China).
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. And all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Disclosure
The authors report no conflicts of interest in this work.