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
Artículo
en Inglés
| 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.
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Índice:
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Asunto principal:
Malaria Falciparum
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Predisposición Genética a la Enfermedad
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Polimorfismo de Nucleótido Simple
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Receptor Toll-Like 9
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Receptor Toll-Like 4
Tipo de estudio:
Estudio de etiología
/
Estudio observacional
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Estudio pronóstico
/
Factores de riesgo
/
Revisiones Sistemáticas Evaluadas
Límite:
Humanos
Idioma:
Inglés
Revista:
Rev. Soc. Bras. Med. Trop
Asunto de la revista:
Medicina Tropical
Año:
2017
Tipo del documento:
Artículo
País de afiliación:
India
Institución/País de afiliación:
North Orissa University/IN
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