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Table 1 A description and main sources of the malaria defense gene variants analyzed

From: Genetics of cerebral malaria: pathogenesis, biomarkers and emerging therapeutic interventions

Gene Converted protein Variations Mechanism Sources
HBB β-globin Sickle hemoglobin heterozygous carriers (HbAS) Acquired host immunity and improved phagocytosis of the ring-parasitized variant RBC’s Cytoadherence and resetting. Disrupted RBC trafficking of parasite proteins. Suppression of the parasite development owing to oxygen-dependent sickle hemoglobin polymerization [158,159,160]
HBB beta-globin Heterozygosity of Beta thalassemia Enhanced antibody binding and subsequent clearance of infected variant RBCs Increased phagocytosis of ring-parasitized variant RBCs [161]
HBA α-globin α-thalassemia (removal of one or more normal 4 genes of α-globin) Increased phagocytosis of infected variant
RBCs by monocytes
Enhanced antibody binding and subsequent
clearance of infected variant RBCs
G6PD Glucose-6-phosphate dehydrogenase (G6PD) G6PD deficiency
(G6PDd) for female heterozygotes
Increased ring parasite phagocytosis of red blood cell because of increased oxidative pressure [2, 166]
CR-1 Complement Receptor 1 Polymorphism of Swain Langley two (Sl2) Decreased Sl2 RBC attachment to PfEMP1 rosetting parasite binding site [167, 168]
FY Chemokines Duffy antigen receptor
FY*ES allele Suppression of Duffy's negative RBC P. vivax invasion by impairment of junction formation [169, 170]
ABO Glycosyltransferase enzyme Blood group O deletion of single nucleotide ABO (rs8176719) Reduced P. falciparum rosetting [2, 75, 171]
ATP2B4 PMCA4 calcium transporter ATP2B4 polymorphisms of single nucleotides (rs4951074 and rs1541255) Changed transcription factors bound to enhancer components of ATP2B4, owing to reduced expression of genes, followed by a disorderly intracellular calcium homeostasis [75, 172]
GYP Glycophorins Making copies of the Dantu blood group GYPB-A encoded by the hybrid genes Inactivation of the invasion of P. falciparum because of excessive Dantu RBC membrane pressure [173,174,175]
IL12-RB2 Complex receptors for Interleukin 23 and 12 Clusters of IL23R-IL12RB2 single nucleotide Immunomodulatory functions in malaria defensive immunity [176, 177]