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

ABSTRACT: 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.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 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.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.

SUBMITTER: Rani A

PROVIDER: S-EPMC6005971 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Role of rs4986790 Polymorphism of <i>TLR4</i> Gene in Susceptibility towards Malaria Infection in the Pakistani Population.

Rani Asima A Nawaz Syed Kashif SK Arshad Muhammad M Irfan Shazia S

Iranian journal of public health 20180501 5

<h4>Background</h4>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 <i>TLR4</i> gene in susceptibility towards malaria, clinical outcomes of the disease and ...[more]

PMID: 29922617

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Project description:Toll-like Receptors (TLRs), such as the TLR4, are genes encoding transmembrane receptors of the same name, which induce a pro- or anti-inflammatory response according to their expression as the host's first line of defense against pathogens, such as infectious ones. Single nucleotide polymorphisms (SNPs) are the most common type of mutation in the human genome and can generate functional modification in genes. The aim of this article is to review in which infectious diseases there is an association of susceptibility or protection by the TLR4 SNP rs4986790. A systematic review and meta-analysis of the literature was conducted in the Science Direct, PUBMED, MEDLINE, and SciELO databases between 2011 and 2021 based on the dominant genotypic model of this SNP for general and subgroup analysis of infectious agent type in random effect. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated for genotypic comparison. I2 statistics were calculated to assess the presence of heterogeneity between studies and funnel plots were inspected for indication of publication bias. A total of 27 articles were included, all in English. Among the results achieved, the categories of diseases that were most associated with the SNP studied were in decreasing order of number of articles: infections by bacteria (29.63%); caused by viruses (22.23%); urinary tract infection-UTI (7.4%), while 11 studies (40.74%) demonstrated a nonsignificant association. In this meta-analysis, a total of 5599 cases and 5871 controls were finalized. The present meta-analysis suggests that there is no significant association between TLR4-rs4986790 SNP and infections (OR = 1,11; 95% CI: 0,75-1,66; p = 0,59), but in the virus subgroup it was associated with a higher risk (OR = 2,16; 95% CI: 1,09-4,30; p = 0,03). The subgroups of bacteria and parasites did not show statistical significance (OR = 0,86; 95% CI: 0,56-1,30; p = 0,47, and no estimate of effects, respectively). Therefore, it has been shown that a diversity of infectious diseases is related to this polymorphism, either by susceptibility or even severity to them, and the receptor generated is also crucial for the generation of cell signaling pathways and immune response against pathogens.

Dataset Information

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

Publications

Role of rs4986790 Polymorphism of <i>TLR4</i> Gene in Susceptibility towards Malaria Infection in the Pakistani Population.

Similar Datasets

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