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

Detalhes bibliográficos
Autor(a) principal: Dhangadamajhi,Gunanidhi
Data de Publicação: 2017
Outros Autores: Kar,Avishek, Rout,Ronnaly, Dhangadamajhi,Prabin
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Revista da Sociedade Brasileira de Medicina Tropical
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822017000200153
Resumo: 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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spelling A meta-analysis of TLR4 and TLR9 SNPs implicated in severe malariaMalariaToll like receptorsMeta-analysisPolymorphisms.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.Sociedade Brasileira de Medicina Tropical - SBMT2017-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822017000200153Revista da Sociedade Brasileira de Medicina Tropical v.50 n.2 2017reponame:Revista da Sociedade Brasileira de Medicina Tropicalinstname:Sociedade Brasileira de Medicina Tropical (SBMT)instacron:SBMT10.1590/0037-8682-0475-2016info:eu-repo/semantics/openAccessDhangadamajhi,GunanidhiKar,AvishekRout,RonnalyDhangadamajhi,Prabineng2017-05-12T00:00:00Zoai:scielo:S0037-86822017000200153Revistahttps://www.sbmt.org.br/portal/revista/ONGhttps://old.scielo.br/oai/scielo-oai.php||dalmo@rsbmt.uftm.edu.br|| rsbmt@rsbmt.uftm.edu.br1678-98490037-8682opendoar:2017-05-12T00:00Revista da Sociedade Brasileira de Medicina Tropical - Sociedade Brasileira de Medicina Tropical (SBMT)false
dc.title.none.fl_str_mv A meta-analysis of TLR4 and TLR9 SNPs implicated in severe malaria
title A meta-analysis of TLR4 and TLR9 SNPs implicated in severe malaria
spellingShingle A meta-analysis of TLR4 and TLR9 SNPs implicated in severe malaria
Dhangadamajhi,Gunanidhi
Malaria
Toll like receptors
Meta-analysis
Polymorphisms.
title_short A meta-analysis of TLR4 and TLR9 SNPs implicated in severe malaria
title_full A meta-analysis of TLR4 and TLR9 SNPs implicated in severe malaria
title_fullStr A meta-analysis of TLR4 and TLR9 SNPs implicated in severe malaria
title_full_unstemmed A meta-analysis of TLR4 and TLR9 SNPs implicated in severe malaria
title_sort A meta-analysis of TLR4 and TLR9 SNPs implicated in severe malaria
author Dhangadamajhi,Gunanidhi
author_facet Dhangadamajhi,Gunanidhi
Kar,Avishek
Rout,Ronnaly
Dhangadamajhi,Prabin
author_role author
author2 Kar,Avishek
Rout,Ronnaly
Dhangadamajhi,Prabin
author2_role author
author
author
dc.contributor.author.fl_str_mv Dhangadamajhi,Gunanidhi
Kar,Avishek
Rout,Ronnaly
Dhangadamajhi,Prabin
dc.subject.por.fl_str_mv Malaria
Toll like receptors
Meta-analysis
Polymorphisms.
topic Malaria
Toll like receptors
Meta-analysis
Polymorphisms.
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2017-03-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822017000200153
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822017000200153
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1590/0037-8682-0475-2016
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Sociedade Brasileira de Medicina Tropical - SBMT
publisher.none.fl_str_mv Sociedade Brasileira de Medicina Tropical - SBMT
dc.source.none.fl_str_mv Revista da Sociedade Brasileira de Medicina Tropical v.50 n.2 2017
reponame:Revista da Sociedade Brasileira de Medicina Tropical
instname:Sociedade Brasileira de Medicina Tropical (SBMT)
instacron:SBMT
instname_str Sociedade Brasileira de Medicina Tropical (SBMT)
instacron_str SBMT
institution SBMT
reponame_str Revista da Sociedade Brasileira de Medicina Tropical
collection Revista da Sociedade Brasileira de Medicina Tropical
repository.name.fl_str_mv Revista da Sociedade Brasileira de Medicina Tropical - Sociedade Brasileira de Medicina Tropical (SBMT)
repository.mail.fl_str_mv ||dalmo@rsbmt.uftm.edu.br|| rsbmt@rsbmt.uftm.edu.br
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