A meta-analysis of TLR4 and TLR9 SNPs implicated in severe malaria
Rev. Soc. Bras. Med. Trop
;
50(2): 153-160, Mar.-Apr. 2017. tab, graf
Article
in English
| LILACS
| ID: biblio-842838
ABSTRACT
Abstract 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 <0.00001, OR = 2.65), suggesting that our results must be considered preliminary. The robustness of -1486C as a risk factor warrants investigation into its functionality in malaria pathogenesis. Further, the lack of an association with the T-1237C variant was weak, and future studies examining more detailed individual data from different ethnic groups are essential for confirmation of its genetic contribution to malaria.
Full text:
Available
Index:
LILACS (Americas)
Main subject:
Malaria, Falciparum
/
Genetic Predisposition to Disease
/
Polymorphism, Single Nucleotide
/
Toll-Like Receptor 9
/
Toll-Like Receptor 4
Type of study:
Etiology study
/
Observational study
/
Prognostic study
/
Risk factors
/
Systematic reviews
Limits:
Humans
Language:
English
Journal:
Rev. Soc. Bras. Med. Trop
Journal subject:
Tropical Medicine
Year:
2017
Type:
Article
Affiliation country:
India
Institution/Affiliation country:
North Orissa University/IN
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