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The role of TLR9 polymorphism in susceptibility to pulmonary tuberculosis.

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Title The role of TLR9 polymorphism in susceptibility to pulmonary tuberculosis.
Not Available
 
Creator Bharti D.
Kumar A.
Mala R.S.
Kumar S.
Ingle H.
Shankar H.
Joshi B.
Raut A.A.
Kumar H.
 
Subject Single-nucleotide polymorphism (SNP)
Pulmonary tuberculosis (PTB)
IP-10
IFNγ
TNFα
Tribes
 
Description Not Available
Mycobacterium tuberculosis (MTB) is the causative agent of pulmonary tuberculosis (PTB), a major health problem that leads to 1.5 million deaths annually. Host genetic factors play a significant role in disease resistance/susceptibility by altering immunity against MTB. Toll-like receptor (TLR) sensors such as TLR2, TLR4, TLR8, and TLR9 are known to play a pivotal role in PTB via modulating sensor expression and/or effector responses. Single-nucleotide polymorphism (SNP) rs187084 (T-1486C) of the TLR9 promoter is associated with various autoimmune disorders and cancers. A recent bioinformatic analysis predicted that the T-1486C SNP is involved in PTB, although its potential role is unclear. To investigate the role of T-1486C in PTB, we stimulated PBMCs with the H37Rv whole cell lysate. We found that the presence of the "C" allele increases the transcriptional activity of the TLR9, which in turn induces high levels of Interferon gamma-induced protein 10 (IP-10), a biomarker for PTB. However, the expression of protective cytokines such as IFNγ and TNFα was observed significantly less with "C" allele in comparison to "T" allele. We further selected three different tribe populations showing differential susceptibility to PTB and performed genotypic analyses for the TLR9 promoter. We found a significantly lower minor allele frequency (MAF) of T-1486C in the Baiga tribe, wherein fewer PTB cases were reported, than that in the Gond and Korku tribes. Collectively, these data suggest that the minor "C" allele at rs187084 locus may be associated with susceptibility to PTB, which may explain the relatively lower PTB rates observed in Baiga tribe members.
Not Available
 
Date 2018-03-22T07:48:24Z
2018-03-22T07:48:24Z
2014-12-01
 
Type Research Paper
 
Identifier Bharti D, Kumar A, Mala RS, Kumar S, Ingle H, Shankar H, Joshi B, Raut AA, Kumar H. (2014). The role of TLR9 polymorphism in susceptibility to pulmonary tuberculosis. Immunogenetics. 2014 Dec;66(12):675-81
0093-7711
http://krishi.icar.gov.in/jspui/handle/123456789/5971
 
Language English
 
Relation Not Available;
 
Publisher Springer Berlin Heidelberg