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

IF 1.8 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics & Personalized Medicine Pub Date : 2023-01-01 DOI:10.2147/PGPM.S404339
Tianchang Lu, Minyi Wang, Nannan Liu, Shuqiong Zhang, Lei Shi, Ling Bao, Feng Luo, Li Shi, Shuyuan Liu, Yufeng Yao
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引用次数: 1

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.

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与抗原加工相关的转运蛋白1基因多态性增加对结核病的易感性。
目的:已知结核(TB)是由宿主免疫反应和分枝杆菌感染之间复杂的相互作用引起的。抗原加工相关转运体(TAP)在结核分枝杆菌(M. tb)抗原的加工和递呈途径中起着重要作用。目的探讨结核分枝杆菌TAP1和TAP2基因与结核分枝杆菌的关系。患者和方法:本研究共纳入449例结核病患者和435例对照,对TAP基因的单核苷酸多态性(snp)以及TAP1和TAP2等位基因进行基因分型。结果:TAP基因与结核病的关联分析显示,TAP1基因中的rs41551515-T与结核病易感性显著相关(P=7.96E-04, OR=4.124, 95% CI: 1.683-10.102),尤其是肺结核(PTB, P=6.84E-04, OR=4.350, 95% CI: 1.727-10.945), TAP1基因中的rs1057141-T-rs1135216-C组合显著增加结核病易感性风险(P=5.51E-05, OR=10.899, 95% CI: 2.555-46.493)。在云南汉族人群中检测到5个新的TAP1等位基因,TAP1*unknown_3等位基因频率(rs41555220-rs41549617-rs1057141-rs1135216-rs1057149-rs41551515: C-A-T-C-C-T)在包括PTB和EPTB亚组在内的所有结核病患者中均显著升高,并与结核病易感风险显著相关。然而,本研究未发现TAP2基因与结核病之间存在关联。结论:rs41551515-T和rs1057141-T-rs1135216-C组合的宿主遗传变异以及TAP1*unknown_3可能在结核病易感性中起关键作用。
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来源期刊
Pharmacogenomics & Personalized Medicine
Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
3.30
自引率
5.30%
发文量
110
审稿时长
16 weeks
期刊介绍: Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.
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