Abstract
IntroductionThis study determined the association of TLR4 Asp299Gly and Thr399Ile with uncomplicated and severe malaria among Nigerian children of similar ethnic background in Lagos. The association of these SNPs with high parasite density, malnutrition, hyperpyrexia and anaemia was also investigated.MethodsGenomic DNA of the study participants was screened for the genotypes of TLR4 Asp299Gly and Thr399Ile by PCR-RFLP. Anthropometric measurement was performed on the Pf infected children stratified into asymptomatic malaria (control), uncomplicated and severe malaria (case). Parasites were detected by light microscopy and Hardy Weinberg Equilibrium (HWE) of SNP genotypes was also determined.ResultsA total of 279 children comprising 182 children (62.1 % male; mean ± SEM age, 57.3 ± 1.7 months) with clinical falciparum malaria and 97 children (55.7 % male; mean ± SEM age, 55.6 ± 2.5 years) with asymptomatic falciparum malaria were enrolled. All the genotypes of both TLR4 SNPs were found in the study population with their minor alleles: 299Gly and 399Ile, found to be 17.6 % and 14.7 % in severe malaria children. Unlike in asymptomatic population, the genotype distribution of TLR4 Asp299Gly SNP was not in HWE in the clinical malaria group but did not condition susceptibility. However, Asp299Gly and Thr399Ile polymorphisms were found to increase the risk of severe malaria 3-fold and 8-fold respectively (P < 0.05). They also increased the risk of severe anaemia, high parasite density and severe malnutrition 3.8 -5.3-fold, 3.3 – 4.4-fold and 4-fold respectively.ConclusionsBased on the above findings, we conclude that TLR4 Asp299Gly and Thr399Ile polymorphisms may modulate susceptibility to severe malaria among Nigerian children of Yoruba ethnic background.
Highlights
This study determined the association of TLR4 Asp299Gly and Thr399Ile with uncomplicated and severe malaria among Nigerian children of similar ethnic background in Lagos
Innate immunity dyregulation has been associated with risk factors and syndromes of severe malaria, including malnutrition, severe anaemia hyperparasitaemia or high parasite density [8, 9]
Further stratification of the clinical malaria cases showed that the frequencies of the minor alleles: 299Gly and 399Ile, of these TLR4 single nucleotide polymorphisms (SNPs) were greater than 10 % (17.6 % and 14.7 % respectively) only in severe malaria children (Table 3 & 4)
Summary
This study determined the association of TLR4 Asp299Gly and Thr399Ile with uncomplicated and severe malaria among Nigerian children of similar ethnic background in Lagos The association of these SNPs with high parasite density, malnutrition, hyperpyrexia and anaemia was investigated. Iwalokun et al Genes and Environment (2015) 37:3 regulation by anti-inflammatory cytokines such as IL-10 in the later phase of infection has been shown to be crucial for parasitaemia control and avertion of host tissue damage and severe malaria [4, 5]. These events have been observed in infected African children who are non-susceptible compared to severe malaria susceptible children [6, 7]. Innate immunity dyregulation has been associated with risk factors and syndromes of severe malaria, including malnutrition, severe anaemia hyperparasitaemia or high parasite density [8, 9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Genes and environment : the official journal of the Japanese Environmental Mutagen Society
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
