Association Between Functional Nucleotide Polymorphisms Up-regulating Transforming Growth Factor beta 1 Expression and Increased Tuberculosis Susceptibility

Zhang, Su1,2; 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 G.4; Chen, Xinchun2; Zhang, Guoliang1,2

2022-03-02

10.1093/infdis/jiaa585

JOURNAL OF INFECTIOUS DISEASES   影响因子和分区

0022-1899

1537-6613

Previous studies demonstrated that transforming growth factor (TGT) beta 1 plays an immunosuppressive role in clinical tuberculosis. However, the contribution of TGF-beta 1 gene polymorphisms to human tuberculosis susceptibility remains undetermined. In this study, we showed that single-nucleotide polymorphisms (SNPs) in TGF-beta 1 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-beta 1 and interleukin 17A production. The mechanistic study showed that rs2317130 C allele affected TGF-beta 1 promoter activity by regulating binding activity to nuclear extracts. These findings provide insights into the pathogenic role of TGF-beta 1 in human tuberculosis and reveal a function for the TGF-beta 1 promoter SNPs in regulating immune responses during Mycobacterium tuberculosis infection.

TGF-beta 1 single-nucleotide polymorphisms Mycobacterium tuberculosis

SCI

英语

第一 ; 通讯

Natural Science Foundation of China[81873958,8192031] ; Shenzhen Scientific and Technological Foundation["JCYJ20180228162321234","JCYJ20180228162511084"] ; National Science and Technology Major Project for Control and Prevention of Major Infectious Diseases of China[2017ZX10103004] ; National Key Research and Development Plan[2019YFC0840602] ; Sanming Project of Medicine in Shenzhen["SZSM201911009","SZSM201612025"]

Immunology ; Infectious Diseases ; Microbiology

Immunology ; Infectious Diseases ; Microbiology

WOS:000763009900012

OXFORD UNIV PRESS INC

IMMUNOLOGY

Web of Science

1.Southern Univ Sci & Technol, Peoples Hosp Shenzhen 3, Natl Clin Res Ctr Infect Dis, Shenzhen, Peoples R China
2.Shenzhen Univ, Dept Pathogen Biol, Guangdong Key Lab Reg Immun & Dis, Sch Med, Shenzhen, Peoples R China
3.Chinese Univ Hong Kong, Shenzhen Longgang Peoples Hosp, Dept Lab Med, Shenzhen 518172, Peoples R China
4.Univ Sydney, Sydney Med Sch, Dept Infect Dis & Immunol, Sydney, NSW, Australia

Zhang, Su,Li, Guobao,Bi, Jing,et al. Association Between Functional Nucleotide Polymorphisms Up-regulating Transforming Growth Factor beta 1 Expression and Increased Tuberculosis Susceptibility[J]. JOURNAL OF INFECTIOUS DISEASES,2022,225(5).

Zhang, Su.,Li, Guobao.,Bi, Jing.,Guo, Qinglong.,Fu, Xiangdong.,...&Zhang, Guoliang.(2022).Association Between Functional Nucleotide Polymorphisms Up-regulating Transforming Growth Factor beta 1 Expression and Increased Tuberculosis Susceptibility.JOURNAL OF INFECTIOUS DISEASES,225(5).

Zhang, Su,et al."Association Between Functional Nucleotide Polymorphisms Up-regulating Transforming Growth Factor beta 1 Expression and Increased Tuberculosis Susceptibility".JOURNAL OF INFECTIOUS DISEASES 225.5(2022).