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

Tianchang Lu,1,* Minyi Wang,1,2,* Nannan Liu,1 Shuqiong Zhang,3 Lei Shi,1 Ling Bao,3 Feng Luo,3 Li Shi,1 Shuyuan Liu,1 Yufeng Yao4 1Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, 650118, People’s Republic of China; 2School of Life Science, Yunnan University, Kunming, 650500, People’s Republic of China; 3Department of Clinical Laboratory, The Third People’s Hospital of Kunming, Kunming, 650041, People’s Republic of China; 4Institute 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*These authors contributed equally to this workCorrespondence: Shuyuan Liu, Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, 650118, People’s Republic of China, Tel +86 871 68334483, Email shuyuanliuoo@gmail.com Yufeng Yao, 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, Tel +86 871 68335632, Email leoyyf@gmail.comPurpose: 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: tuberculosis, association, TAP gene, polymorphism, novel allele