Association of toll like receptors polymorphism (TLR1-rs4833095, TLR1-rs5743611, TLR6-rs5743810, TLR6-rs5743809, TLR4-rs4986790, TLR4-rs4986791, TLR9 rs187084) with clinical outcome of malaria among children in Ibadan, Southwest Nigeria.

Abstract

Different genetic polymorphisms, particularly in the erythrocyte receptors and immune response-related genes, have been implicated in the development of malaria. With the first immune response to Plasmodium falciparum related to the activity of toll-like receptors (TLRs), we investigated the association of TLR polymorphisms with the clinical outcome of malaria among 662 children in Ibadan, Nigeria. The participants were genotyped for TLR1-rs5743611, TLR1-rs4833095, TLR4-rs4986791, TLR4-rs4986790, TLR6-rs5743810, TLR9-rs187084 and TLR9-rs5743809 using TaqMan real-time PCR probes and analyzed using the Sequenom iPLEX platform. Statistical analyses were performed using PLINK 2.0, Haploview 4.2 and SPSS® 20.0. Overall, the TLR genes were consistent with the Hardy-Weinberg equilibrium. The minor allelic frequency (MAF) of TRL1-rs4833095, TLR4-rs4986790, TLR4-rs4986791, TLR9-rs187084, TLR9-rs5743809 was 0.094, 0.089, 0.011, 0.288, and 0.044, respectively. The CT genotype of TLR1-rs4833095 was significantly associated with increased susceptibility to clinical malaria. Similarly, the GA and CT genotypes of TLR4-rs4986790 and TLR4-rs4986791, respectively, were linked to susceptibility to complicated malaria. TLR9-rs187084 CT was associated with the development of uncomplicated malaria, while TLR6-rs5743809 showed no significant association with malaria. Notably, TLR1-rs5743611 and TLR6-rs5743810 were monomorphic in the population. This study, pioneering in its exploration of TLR polymorphisms among Yorubas', underscores the need for expansive, large-scale investigations involving diverse TLR polymorphisms across multiple malaria-endemic populations.