Genetic variants of TLR4, including the novel variant, rs5030719, and related genes are associated with susceptibility to clinical malaria in African children.
Malar J
; 22(1): 177, 2023 Jun 07.
Article
em En
| MEDLINE
| ID: mdl-37287037
ABSTRACT
BACKGROUND:
Malaria is a deadly disease caused by Plasmodium spp. Several blood phenotypes have been associated with malarial resistance, which suggests a genetic component to immune protection.METHODS:
One hundred and eighty-seven single nucleotide polymorphisms (SNPs) in 37 candidate genes were genotyped and investigated for associations with clinical malaria in a longitudinal cohort of 349 infants from Manhiça, Mozambique, in a randomized controlled clinical trial (RCT) (AgeMal, NCT00231452). Malaria candidate genes were selected according to involvement in known malarial haemoglobinopathies, immune, and pathogenesis pathways.RESULTS:
Statistically significant evidence was found for the association of TLR4 and related genes with the incidence of clinical malaria (p = 0.0005). These additional genes include ABO, CAT, CD14, CD36, CR1, G6PD, GCLM, HP, IFNG, IFNGR1, IL13, IL1A, IL1B, IL4R, IL4, IL6, IL13, MBL, MNSOD, and TLR2. Of specific interest, the previously identified TLR4 SNP rs4986790 and the novel finding of TRL4 SNP rs5030719 were associated with primary cases of clinical malaria.CONCLUSIONS:
These findings highlight a potential central role of TLR4 in clinical malarial pathogenesis. This supports the current literature and suggests that further research into the role of TLR4, as well as associated genes, in clinical malaria may provide insight into treatment and drug development.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptor 4 Toll-Like
/
Malária
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Malar J
Assunto da revista:
MEDICINA TROPICAL
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Austrália