期刊
CYTOKINE
卷 127, 期 -, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2019.154956
关键词
IL17A; Polymorphism; Tuberculosis; Genotype; Therapy
资金
- Natural Science Foundation of China [81525016, 81772145]
- Thirteenth-Fifth Mega-Scientific Projects on prevention and treatment of AIDS, viral hepatitis and other infectious diseases [2017ZX10201301]
- Natural Science Foundation of Guangdong province [2017A030313592]
- Shenzhen Scientific and Technological Foundation [JCYJ20160427152106244]
Th17 cells play a key role in immunity against Mycobacterium tuberculosis, our previous research showed that reduced Th17 responses were associated with the severe outcome of Mtb infection. The associations between IL17A polymorphisms and susceptibility of TB has been reported, but the results are inconsistent and the underlying mechanisms is unknown. In this study, we identified a genetic variation (rs8193036) in the promoter region of IL17A is associated with susceptibility to TB. The minor allele T frequency of rs8193036 was significantly different between patients with active TB (29.7%) and healthy controls (32.3%) (OR = 0.81; 95%CI, 0.71-0.93; P = 0.0026). Peripheral blood mononuclear cells from individuals carrying rs8193036CC genotypes produced significantly lower amount of IL17A upon CD3/28 stimulation compared to the individuals carrying rs8193036TT genotypes. Functional assay by reporter luciferase activity and EMSA demonstrated that rs8193036C exhibited significantly lower promotor transcription activities. In conclusion, our study confirmed that IL17A (rs8193036) is a functional SNP that could regulate gene expression though influencing transcription factor binding activity.
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