Role of rs4986790 Polymorphism of TLR4 Gene in Susceptibility towards Malaria Infection in the Pakistani Population.

Background: Toll-like receptors (TLRs) of the human immune mechanism play important role in the detection of invading pathogens. TLRs specifically recognize the pathogen-associated molecular patterns (PAMPs) from pathogens and start the effective response. Single nucleotide polymorphisms (SNPs) in the TLRs can mediate their functions. Present study evaluated the importance of rs4986790 polymorphism of TLR4 gene in susceptibility towards malaria, clinical outcomes of the disease and responsible species of malaria.

Methods: Blood samples of 228 malaria patients and 226 healthy volunteers were selected for the study. Sample collection was completed during Sep 2013 to Sep 2015 from different hospitals of Punjab, Pakistan. Patient's samples were divided into P. vivax group and P. falciparum group on the basis of causative species of Plasmodium . Malaria samples were also divided into mild and severe malaria group based on clinical outcomes of the disease according to WHO criteria. Healthy individuals were placed in the control group. Whole blood was used for the isolation of DNA. Genomic DNA was isolated and amplification of targeted SNP was performed using allele-specific PCR.

Results: Results indicate the protective role of AA genotype against the susceptibility of P. vivax infection, OR: 0.5, 95%CI: 0.285-0.876, P =0.038.

Conclusion: rs4986790 polymorphism of TLR4 gene modulates the susceptibility towards P. vivax infection. AA genotype is found to be protective against the development of P. vivax infection in the local population of Pakistan.