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 | |
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 | |
CR-1 | Complement Receptor 1 | Polymorphism of Swain Langley two (Sl2) | Decreased Sl2 RBC attachment to PfEMP1 rosetting parasite binding site | |
FY | Chemokines Duffy antigen receptor (DARC) | FY*ES allele | Suppression of Duffy's negative RBC P. vivax invasion by impairment of junction formation | |
ABO | Glycosyltransferase enzyme | Blood group O deletion of single nucleotide ABO (rs8176719) | Reduced P. falciparum rosetting | |
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 | |
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 | |
IL12-RB2 | Complex receptors for Interleukin 23 and 12 | Clusters of IL23R-IL12RB2 single nucleotide | Immunomodulatory functions in malaria defensive immunity |