Association between Toll-like Receptor 4 (TLR4) Genetic Polymorphisms and Susceptibility to Pulmonary Tuberculosis

Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) are the members of the Toll-like receptor family and play important roles in recognition and subsequent immune response against mycobacteria. Two functional polymorphisms for TLR2 (Arg677Trp, C à T Arg753Gln, G à A) and TLR4 (Asp299Gly, A à G Thr399Ile, C à T) genes have been associated with a negative influence on their function, which may affect the innate host response to mycobacteria. The aim of this study was to investigate TLR2 and TLR4 genetic variants in a sample of Iranian patients with pulmonary tuberculosis compared to healthy controls. Patients and A case-control study was carried out on 96 patients and 122 ethnically matched healthy controls. Genotyping protocol was based on a novel polymerase chain reaction sequence-specific primers (PCR-SSP) method. Allelic and genotypic distribution of mentioned polymorphisms were compared by using Fischer’s exact test between patient and control groups. The prevalence of TLR4 variant alleles (Gly299 and Ile399) was significantly higher among patients compared to control individuals (Gly299: 7.2% vs. 2.9%, OR=2.66, P=0.028 and Ile399: 4.2% vs. 0.8%, OR= 5.26, P value = 0.022). Regarding TLR2 Arg753Gln polymorphism, no significant difference was observed between patient and control groups (0% vs.0.8%, P>0.05). The other TLR2 polymorphism (Arg677Trp) was not found in any of the studied subjects. Our data demonstrates that TLR4 genetic polymorphisms may influence the risk of developing tuberculosis after exposure to mycobacterium. In addition, very low frequency of TLR2 genetic variants is revealed in Iranian population.