Association of Toll-like Receptors 1, 2, 4, 6, 8, 9 and 10 Genes Polymorphisms and Susceptibility to Pulmonary Tuberculosis in Sudanese Patients.

ABSTRACT

Background: Genetic factors are important contributors to the development of a wide range of complex disease. Polymorphisms in genes encoding for toll-like receptors (TLRs) usually influence the efficiency of the immune response to infection and are associated with disease susceptibility and progression. Therefore, we aim to describe the first association between TLR1, TLR2, TLR4 TLR6, TLR8, TLR9 and TLR10 genes polymorphisms and susceptibility to pulmonary tuberculosis (PTB) in Sudanese patients. Methodology: Here we performed a case study which included 160 tuberculosis patients and 220 healthy matched controls from Sudan. In the study population, we evaluated the possible association between 86 markers in TLR1, TLR2, TLR4 TLR6, TLR8, TLR9 and TLR10 genes polymorphisms and susceptibility to PTB disease in Sudanese population using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results: From our results it appeared that in the PTB population the TLR1 (rs5743557, rs4833095, rs5743596), TLR2 (rs5743704, rs5743708, rs3804099), TLR4 (rs4986790, rs4986791), TLR6 (rs5743810), TLR8 (rs3764879, rs3764880), TLR9 (rs352165, rs352167, rs187084) and TLR10 (rs4129009) were significantly more often encountered (p<0.0001) than in the control population and were associated with PTB in the Sudanese population. For the other polymorphisms tested, no association with PTB was found in the population tested. Conclusion: The work describes novel mutations in TLR1, TLR2, TLR4, TLR6, TLR8, TLR9 and TLR10 genes and their association with PTB infection in Sudanese population. These results will enhance our ability to determine the risk of developing the disease by targeting specific TLR pathways to reduce the severity of the disease. Future studies are needed in a larger sample to replicate our findings and understand the mechanism of association of TLR polymorphism in PTB.