ArticlePloS one2013
Epistatic Interactions between apolipoprotein E and hemoglobin S Genes in regulation of malaria parasitemia.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- Changes in Lipid Profile Secondary to Asymptomatic Malaria in Migrants from Sub-Saharan Africa: A Retrospective Analysis of a 2010-2022 Cohort.Tropical medicine and infectious disease · 2025Article
- Evolutionary history of sickle-cell mutation: implications for global genetic medicine.Human molecular genetics · 2021Review
- The Genetic Variability ofGenes · 2019Review
- Evidence of strain structure inProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Serum Lipids and Lipoproteins During Uncomplicated Malaria: A Cohort Study in Lambaréné, Gabon.The American journal of tropical medicine and hygiene · 2017Article
- The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer's disease of humans and mice.Neurobiology of aging · 2016Article
- Quantitative trait locus analysis of parasite density reveals that HbS gene carriage protects severe malaria patients against Plasmodium falciparum hyperparasitaemia.Malaria journal · 2015Article
- Apolipoprotein E (ApoE) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy?Proceedings. Biological sciences · 2015Article
- Rapid identification of apolipoprotein E genotypes by high-resolution melting analysis in Chinese Han and African Fang populations.Experimental and therapeutic medicine · 2015Article
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Authors and funding
9 authors at 2 institutions in 3 countries.
Funding
Abstract
Apolipoprotein E is a monomeric protein secreted by the liver and responsible for the transport of plasma cholesterol and triglycerides. The APOE gene encodes 3 isoforms Ɛ4, Ɛ3 and Ɛ2 with APOE Ɛ4 associated with higher plasma cholesterol levels and increased pathogenesis in several infectious diseases (HIV, HSV). Given that cholesterol is an important nutrient for malaria parasites, we examined whether APOE Ɛ4 was a risk factor for Plasmodium infection, in terms of prevalence or parasite density. A cross sectional survey was performed in 508 children aged 1 to 12 years in Gabon during the wet season. Children were screened for Plasmodium spp. infection, APOE and hemoglobin S (HbS) polymorphisms. Median parasite densities were significantly higher in APOE Ɛ4 children for Plasmodium spp. densities compared to non-APOE Ɛ4 children. When stratified for HbS polymorphisms, median Plasmodium spp. densities were significantly higher in HbAA children if they had an APOE Ɛ4 allele compared to those without an APOE Ɛ4 allele. When considering non-APOE Ɛ4 children, there was no quantitative reduction of Plasmodium spp. parasite densities for HbAS compared to HbAA phenotypes. No influence of APOE Ɛ4 on successful Plasmodium liver cell invasion was detected by multiplicity of infection. These results show that the APOE Ɛ4 allele is associated with higher median malaria parasite densities in children likely due to the importance of cholesterol availability to parasite growth and replication. Results suggest an epistatic interaction between APOE and HbS genes such that sickle cell trait only had an effect on parasite density in APOE Ɛ4 children. This suggests a linked pathway of regulation of parasite density involving expression of these genes. These findings have significance for understanding host determinants of regulation of malaria parasite density, the design of clinical trials as well as studies of co-infection with Plasmodium and other pathogens.
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