A meta-analysis of TLR4 and TLR9 SNPs implicated in severe malaria
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , |
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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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 |
eu_rights_str_mv |
openAccess |
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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1752122160615260160 |