Protective Association of TLR6 rs5743810 with Pulmonary Tuberculosis in the Population of JAMMU Region

Tuberculosis (TB) is an international public health problem that results in preventable deaths each year. About 10% of those infected develop tuberculosis, indicating that host defense factors play a significant role in the progression to active disease. Polymorphic variants in the genes determine genetic diversity among populations. Many studies have revealed that single nucleotide polymorphisms (SNPs) in the genes coding for the innate immune molecules can affect the susceptibility and outcome of various diseases. Till date, Jammu & Kashmir state has largely remained unexplored in terms of genetic diversity. Toll-like receptors (TLRs) are fundamental elements of the innate immune system. TLRs identify microbial components that are conserved in pathogens and start the necessary inflammatory immune responses required for activation of adaptive immunity. Studies among populations with polymorphisms in TLR signaling genes can elucidate the connection between TLRs and human diseases. The present study is designed to find out the association of SNPs in TLR1, TLR2, TLR4 and TLR6 genes with pulmonary tuberculosis within the Dogra population of Jammu and Kashmir. This is conducted as a case-control study that includes 150 pulmonary tuberculosis (PTB) and 130 Healthy controls. SNP Genotyping for exploring the polymorphisms is done by using Sanger sequencing. T allele in TLR6 (rs5743810) showed a protective role in TB infection ( p = 0.0011, OR 0.16 95% CI 0.055-0.48). However, the data showed no significant association of TLR1 (rs4833095) , TLR2 ( rs3804099 ) and TLR4 ( rs4986790) with PTB in the Dogra population of Jammu region. Our data gave new insights into the role of TLR6 in M.tuberculosis defense and showed that TLR6 variant rs5743810 is associated with protection against TB in Dogra population of Jammu region. More studies on the larger ethnically diverse patient cohorts may help to validate the possible effect of these polymorphisms on the susceptibility to pulmonary TB.