ArticlePloS one2011
Polymorphisms in the RNASE3 gene are associated with susceptibility to cerebral malaria in Ghanaian children.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 20 citations in OpenAlex.
- Human blood neutrophils generate ROS through FcγR-signaling to mediate protection against febrile P. falciparum malaria.Communications biology · 2023Article
- Emerging Evidence for Pleiotropism of Eosinophils.International journal of molecular sciences · 2021Review
- Human RNase3 immune modulation by catalytic-dependent and independent modes in a macrophage-cell line infection model.Cellular and molecular life sciences : CMLS · 2021Article
- Eosinophils Suppress the Migration of T Cells Into the Brain ofFrontiers in immunology · 2021Article
- Haplotype of RNASE 3 polymorphisms is associated with severe malaria in an Indian population.Molecular biology reports · 2020Article
- Genetic variants of RNASE3 (ECP) and susceptibility to severe malaria in Senegalese population.Malaria journal · 2018Article
- Immune Modulation by Human Secreted RNases at the Extracellular Space.Frontiers in immunology · 2018Review
- Rapid Evolution of Primate Type 2 Immune Response Factors Linked to Asthma Susceptibility.Genome biology and evolution · 2017Article
- The Ribonuclease A Superfamily in Humans: Canonical RNases as the Buttress of Innate Immunity.International journal of molecular sciences · 2016Review
- Reductions in microfilaridermia by repeated ivermectin treatment are associated with lower Plasmodium-specific Th17 immune responses in Onchocerca volvulus-infected individuals.Parasites & vectors · 2015Article
- Article
- Eosinophils: changing perspectives in health and disease.Nature reviews. Immunology · 2013Review
- Fc γ receptor IIIB (FcγRIIIB) polymorphisms are associated with clinical malaria in Ghanaian children.PloS one · 2012Article
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCerebral malaria (CM) is the most severe outcome of Plasmodium falciparum infection and a major cause of death in children from 2 to 4 years of age. A hospital based study in Ghana showed that P. falciparum induces eosinophilia and found a significantly higher serum level of eosinophil cationic protein (ECP) in CM patients than in uncomplicated malaria (UM) and severe malaria anemia (SA) patients. Single nucleotide polymorphisms (SNPs) have been described in the ECP encoding-gene (RNASE3) of which the c.371G>C polymorphism (rs2073342) results in an arginine to threonine amino acid substitution p.R124T in the polypeptide and abolishes the cytotoxicity of ECP. The present study aimed to investigate the potential association between polymorphisms in RNASE3 and CM. METHODOLOGY/PRINCIPAL
findingsThe RNASE3 gene and flanking regions were sequenced in 206 Ghanaian children enrolled in a hospital based malaria study. An association study was carried out to assess the significance of five SNPs in CM (n=45) and SA (n=56) cases, respectively. The two severe case groups (CM and SA) were compared with the non-severe control group comprising children suffering from UM (n=105). The 371G allele was significantly associated with CM (p=0.00945, OR=2.29, 95% CI=1.22-4.32) but not with SA. Linkage disequilibrium analysis demonstrated significant linkage between three SNPs and the haplotype combination 371G/*16G/*94A was strongly associated with susceptibility to CM (p=0.000913, OR=4.14, 95% CI=1.79-9.56), thus, defining a risk haplotype. The RNASE3 371GG genotype was found to be under frequency-dependent selection. CONCLUSIONS/SIGNIFICANCE: The 371G allele of RNASE3 is associated with susceptibility to CM and forms part of a risk associated haplotype GGA defined by the markers: rs2073342 (G-allele), rs2233860 (G-allele) and rs8019343 (A-allele) respectively. Collectively, these results suggest a hitherto unrecognized role for eosinophils in CM pathogenesis.
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