Association Between Functional Nucleotide Polymorphisms Up-regulating Transforming Growth Factor β1 Expression and Increased Tuberculosis Susceptibility

Author:

Zhang Su12,Li Guobao1,Bi Jing1,Guo Qinglong1,Fu Xiangdong1,Wang Wenfei2,Liu Shuyan1,Xiao Guohui1,Ou Min1,Zhang Juanjuan1,He Xing1,Li Fang1,Li Guanqiang3,Feng Carl G4,Chen Xinchun2,Zhang Guoliang12

Affiliation:

1. National Clinical Research Center for Infectious Diseases, The Third People’s Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, China

2. Guangdong Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, China

3. Department of Laboratory Medicine, Shenzhen Longgang People’s Hospital, Chinese University of Hong Kong, China

4. Department of Infectious Diseases and Immunology, Sydney Medical School, University of Sydney, Sydney, Australia

Abstract

Abstract Previous studies demonstrated that transforming growth factor (TGT) β1 plays an immunosuppressive role in clinical tuberculosis. However, the contribution of TGF-β1 gene polymorphisms to human tuberculosis susceptibility remains undetermined. In this study, we showed that single-nucleotide polymorphisms (SNPs) in TGF-β1 gene were associated with increased susceptibility to tuberculosis in the discovery cohort (1533 case patients and 1445 controls) and the validation cohort (832 case patients and 1084 controls), and 2 SNPs located in the promoter region (rs2317130 and rs4803457) are in strong linkage disequilibrium. The SNP rs2317130 was associated with the severity of tuberculosis. Further investigation demonstrated that rs2317130 CC genotype is associated with higher TGF-β1 and interleukin 17A production. The mechanistic study showed that rs2317130 C allele affected TGF-β1 promoter activity by regulating binding activity to nuclear extracts. These findings provide insights into the pathogenic role of TGF-β1 in human tuberculosis and reveal a function for the TGF-β1 promoter SNPs in regulating immune responses during Mycobacterium tuberculosis infection.

Funder

Natural Science Foundation of China

Shenzhen Scientific and Technological Foundation

National Science and Technology Major Project for Control and Prevention of Major Infectious Diseases of China

National Key Research and Development Plan

Sanming Project of Medicine in Shenzhen

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Challenges and the Way forward in Diagnosis and Treatment of Tuberculosis Infection;Tropical Medicine and Infectious Disease;2023-01-28

2. Tuberculosis;Pulmonomics: Omics Approaches for Understanding Pulmonary Diseases;2023

3. Research progress on genetic control of host susceptibility to tuberculosis;Journal of Zhejiang University (Medical Sciences);2022-12-01

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