Genetic Factors in Malaria Susceptibility and Severity
Summary
Malaria remains a leading cause of morbidity and mortality in tropical regions, and inter-individual differences in disease outcome are strongly influenced by host genetics. Classic erythrocyte variants such as sickle haemoglobin, thalassaemias and glucose-6-phosphate dehydrogenase deficiency impede parasite invasion or growth, thereby reducing the risk of severe anaemia and cerebral manifestations. Beyond red-cell traits, polymorphisms in genes governing innate and adaptive immunity modulate the magnitude and timing of inflammatory responses. Variants in cytokine promoters, Toll-like receptors and adhesion molecules can either enhance parasite clearance or precipitate immunopathology, shaping susceptibility to high-density parasitaemia and organ dysfunction. Recent technological advances in genome-wide association studies and targeted sequencing have uncovered novel loci under strong selective pressure in endemic populations, revealing complex patterns of balancing selection and gene–environment interactions. Understanding these genetic determinants is critical for refining vaccine design, optimising chemopreventive regimens and tailoring interventions to genetically diverse communities.
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Genetic Factors in Malaria Susceptibility and Severity publication trend
The graph below shows the total number of articles in genetic factors in malaria susceptibility and severity across all publications each year (not limited to Nature Index journals).
Technical terms
Polymorphism: A single-nucleotide or structural variation in DNA sequence among individuals.
Cis-regulatory variant: A non-coding alteration that affects the transcriptional activity of a nearby gene.
Fc gamma receptor (FcγR): A cell-surface protein that binds the Fc portion of immunoglobulin G and mediates phagocytosis.
Cytokine: A secreted signalling protein that orchestrates immune and inflammatory responses.
Genome-wide association study (GWAS): A high-throughput analysis to identify genetic variants linked to disease traits across the entire genome.
References
- Cytokine gene polymorphisms implicated in the pathogenesis of Plasmodium falciparum infection outcome. Frontiers in Immunology (2024).
- A Non-Coding Fc Gamma Receptor Cis-Regulatory Variant within the 1q23 Gene Cluster Is Associated with Plasmodium falciparum Infection in Children Residing in Burkina Faso. International Journal of Molecular Sciences (2023).
- The Host Genetic Diversity in Malaria Infection. Journal of Tropical Medicine (2012).
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