A meta-analysis of TLR4 and TLR9 SNPs implicated in severe malaria

Toll-like receptors (TLRs) are critical mediators of the inflammatory response to malarial infection, and gene polymorphisms affecting TLR function may be partially responsible for inter-individual variation in disease manifestation. However, there are inconsistencies in the associations of common g...

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Bibliographic Details
Published in:Revista da Sociedade Brasileira de Medicina Tropical 2017-03, Vol.50 (2), p.153-160
Main Authors: Dhangadamajhi, Gunanidhi, Kar, Avishek, Rout, Ronnaly, Dhangadamajhi, Prabin
Format: Article
Language:English
Subjects:
Adults
Alleles
Genetic Predisposition to Disease - genetics
Genetic variance
Genotype
Humans
Immune system
Inflammation
Inflammatory response
Malaria
Malaria, Falciparum - genetics
Meta-analysis
Minority & ethnic groups
Pathogenesis
Plasmodium falciparum
Polymorphism
Polymorphism, Single Nucleotide
Polymorphisms
Proteins
Receptors
Risk Factors
Severity of Illness Index
Single-nucleotide polymorphism
TLR4 protein
TLR9 protein
Toll like receptors
Toll-Like Receptor 4 - genetics
Toll-Like Receptor 9 - genetics
TROPICAL MEDICINE
Vector-borne diseases
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Summary:Toll-like receptors (TLRs) are critical mediators of the inflammatory response to malarial infection, and gene polymorphisms affecting TLR function may be partially responsible for inter-individual variation in disease manifestation. However, there are inconsistencies in the associations of common genetic variants of TLR4 (D299G) and TLR9 (T-1237C and T-1486C) with malaria outcome. A comprehensive search was conducted to identify relevant and independent Plasmodium falciparum-infected case-control studies, and meta-analysis including six studies for each SNP was performed to obtain more precise estimates of the pooled effects of these variants. The results showed significant associations of the -1486C allele with the risk of severe malaria in allele contrast (T vs. C, p = 0.004, OR = 1.26) and homozygous (TT vs. CC, p = 0.03, OR = 1.51) genetic models. There was no association between the D299G or T-1237C variants and uncomplicated or severe malaria using any of the genetic models tested. However, in stratified analysis, -1237C was associated with the risk of severe malaria in Indian adults (TT vs. TC, p = 0.06, OR = 2.13; TT vs. TC+CC, p
ISSN:0037-8682
1678-9849
1678-9849
0037-8682
DOI:10.1590/0037-8682-0475-2016