Association of TLR2 T597C, TLR4 A896G, and TLR9 G1174A gene polymorphisms with risk of pulmonary tuberculosis in the Ethiopian population: A case-control study

BACKGROUND: Toll-like receptor genes have been extensively researched for their role in the susceptibility to pulmonary tuberculosis across different populations. The relationship between variations in toll-like receptor genes and additional risk factors for pulmonary tuberculosis is not well understood, because of the complex interplay between genetic predispositions and environmental influences. This study aimed to elucidate the association of TLR2 T597C, TLR4 A896G, and TLR9 G1174A gene polymorphisms with the risk of developing pulmonary tuberculosis. METHODS: A total of 306 samples - 153 patients with pulmonary tuberculosis and 153 age- and sex-matched healthy controls were selected using a consecutive sampling technique. Clinical and biochemical variables were measured to assess the associated risk factors. Deoxyribonucleic acid was isolated from blood samples, and the TLR2, TLR4, and TLR9 genotypes were identified using polymerase chain reaction-restriction fragment length polymorphism and analyzed by agarose gel electrophoresis. RESULTS: Our analysis showed that the TLR2-CC genotype (OR = 3.82; 95% CI = 1.79-8.16; P < 0.001) and C allele (OR=2.12; 95%CI: 1.42-3.10; P < 0.001), the TLR4-GG genotype (OR=3.18; 95%CI: 1.71-5.92; P < 0.001) and G allele (OR=2.25; 95%CI: 1.61-3.14; P < 0.001), and the TLR9-AA genotype (OR=2.00; 95%CI: 1.09-3.68; P = 0.025) and A allele (OR=1.60; 95%CI: 1.15-2.21; P < 0.001) is significantly associated in patients than in controls, suggesting their potential role as genetic risk factors for the development of pulmonary tuberculosis. Combined genotype analysis revealed that individuals carrying all three risk genotypes (CC-GG-AA) significantly associated with increased PTB risk. Multivariable analysis showed that HIV co-infection and malnutrition were independent predictors of pulmonary tuberculosis. CONCLUSION: The TLR2 T597C gene of the CC genotype and the C allele, the TLR4 A896G genes of the GG genotype and the G allele, and the TLR9 G1174A genes of the AA genotype and the A allele are associated with increased risk of pulmonary tuberculosis among the Ethiopian patients under study.