Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 225, Issue 5, Pages 825-835Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiaa585
Keywords
TGF-beta 1; single-nucleotide polymorphisms; Mycobacterium tuberculosis
Categories
Funding
- 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]
Ask authors/readers for more resources
This study found that SNPs in the TGF-beta 1 gene are associated with tuberculosis susceptibility and disease severity. Specifically, the rs2317130 CC genotype is linked to higher levels of TGF-beta 1 and interleukin 17A production. These findings suggest a role for TGF-beta 1 promoter SNPs in regulating immune responses during Mycobacterium tuberculosis infection.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available