Toll Like Receptor-4 Gene Polymorphism and Susceptibility to Pulmonary Tuberculosis

Tuberculosis (TB) affects human life globally for a long time. The difference in clinical outcome of infection suggests that host genetic makeup is responsible for such variability. Toll like receptors (TLRs) are pattern recognition receptors and have a significant role in mycobacterial recognition by the innate immune system. TLR-4 is the key receptor in initiation of innate immunity against M. tuberculosis. This study investigated whether variants in TLR-4 896A/G (Asp299Gly) and TLR-4 1196C/T (Thr399Ile) genes are related with susceptibility or resistance to pulmonary tuberculosis (PTB) in Saudi population. Genotyping of TLR-4 896A/G, TLR-4 1196C/T gene was performed by polymerase chain reaction followed by restriction fragment length polymorphism (PCR -RFLP) in 60 PTB patients and 60 control subjects. The A allele at (896A/G) was more frequent in the control group while G allele was more common in PTB patients. The frequency of T allele of (1196C/T) polymorphism was significantly increased in PTB patients as compared to the control group (P < 0.001; Odds ratio (OR) 2.79, 95% Confidence interval (CI) 1.65-4.72). A trend toward increased frequency of TT and CT genotypes of TLR4 at (1196C/T) were also observed in PTB patients as compared to control group (48.3% vs. 26, 7%, and 21.7% vs. 15%), respectively. This study suggests that that TLR4 polymorphism especially TLR4 rs4986791 may be associated with increase susceptibility to pulmonary tuberculosis, and C allele of rs4986791 is a promising protective factor for tuberculosis susceptibility in Saudi population.