Polymorphisms of ATP2B4 encoding an ubiquitous Ca(2+) pump protect against severe childhood malaria. We assessed the influence of a main polymorphism (rs10900585) on malaria among 834 delivering Ghanaian women. In homozygous primiparae, the odds of placental Plasmodium falciparum infection were reduced by 64%. No influence of the polymorphism on parasite density, low birth weight, or preterm delivery was discernible. However, malarial anemia was greatly reduced in primiparous carriers of the variant allele, paralleling the reduced impact of malaria on hemoglobin levels in this group. A common ATP2B4 polymorphism protects against malaria in pregnancy and related maternal anemia, suggesting ATP2B4 variant associated protection not to be limited to severe childhood malaria.
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http://dx.doi.org/10.1093/infdis/jit070 | DOI Listing |
PLoS One
January 2025
Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary.
Front Cell Infect Microbiol
January 2024
Wellcome Sanger Institute, Cambridge, United Kingdom.
parasites have a complex life cycle, but the most clinically relevant stage of the disease is the invasion of erythrocytes and the proliferation of the parasite in the blood. The influence of human genetic traits on malaria has been known for a long time, however understanding the role of the proteins involved is hampered by the anuclear nature of erythrocytes that makes them inaccessible to genetic tools. Here we overcome this limitation using stem cells to generate erythroid cells with an differentiation protocol and assess parasite invasion with an adaptation of flow cytometry to detect parasite hemozoin.
View Article and Find Full Text PDFElife
June 2023
Centre for Geographic Medicine Research (Coast), KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.
Background: The long co-evolution of and has resulted in the selection of numerous human genetic variants that confer an advantage against severe malaria and death. One such variant is the Dantu blood group antigen, which is associated with 74% protection against severe and complicated malaria infections in homozygous individuals, similar to that provided by the sickle haemoglobin allele (HbS). Recent studies suggest that Dantu exerts this protection by increasing the surface tension of red blood cells, thereby impeding the ability of merozoites to invade them and reducing parasite multiplication.
View Article and Find Full Text PDFMalar J
February 2023
Aix Marseille Univ, INSERM, TAGC, MarMaRa Institute, Marseille, France.
Background: Genome-wide association studies have identified ATP2B4 as a severe malaria resistance gene. Recently, 8 potential causal regulatory variants have been shown to be associated with severe malaria.
Methods: Genotyping of rs10900585, rs11240734, rs1541252, rs1541253, rs1541254, rs1541255, rs10751450, rs10751451 and rs10751452 was performed in 154 unrelated individuals (79 controls and 75 mild malaria patients).
Background: Polymorphisms in ATP2B4 coding for PMCA4b, the primary regulator of erythrocyte calcium concentration, have been shown by GWAS and cross-sectional studies to protect against severe malaria but the mechanism remains unknown.
Methods: Using a recall-by-genotype design, we investigated the impact of a common haplotype variant in ATP2B4 using in vitro assays that model erythrocyte stage malaria pathogenesis. Ninety-six donors representing homozygote (carriers of the minor allele, C/C), heterozygote (T/C) and wildtype (T/T) carriers of the tagging SNP rs1541252 were selected from a cohort of over 12,000 participants in the Keneba Biobank.
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