Table 1.
Genetic mutations involved in susceptibility/resistance to P.falciparum malaria
| Gene (Symbol) | Phenotype | Proposed protective mechanisms | References |
|---|---|---|---|
| Haemoglobin C (HbC) |
↓UM & ↓SM | Reduced cyto-adherence of infected erythrocytes | [29,47] |
| Haemoglobin E (HbE) |
↓SM, ↓parasitaemia | Reduced erythrocyte invasion by merozoites, lower intra-erythrocytic parasite growth, and enhanced phagocytosis of infected erythrocytes. | [48,49] |
| Haemoglobin S (HbS) |
↓UM & ↓SM | Selective sickling of infected sickle trait erythrocytes leading to enhanced clearance by the spleen. Reduced erythrocyte invasion, early phagocytosis, and inhibited parasite growth under oxygen stress in venous micro vessels. Enhancement of innate and acquired immunity. | [7,50] |
| α-thalassaemia (α-thal) |
↓SM & ↓SMA | Reduced resetting. Increased micro-erythrocyte count in homozygotes reduces the amount of haemoglobin lost for given parasite density, thus protecting against severe anaemia. | [51-53] |
| β-thalassaemia (β-thal) |
↓SM | [54,55] | |
| Glucose-6-Phosphate dehydrogenase (G6PD) | ↓UM & ↓SM | Increased vulnerability of the G6PD deficient erythrocyte to oxidant stress causes its protection against parasitization. | [56-59] |
| Pyruvate kinase (PKLR) | ↓parasitaemia | Invasion defect of erythrocytes and preferential macrophage clearance of ring-stage-infected erythrocytes. | [60] |
| Ovalocytosis (SLC4A1) | ↓SM & ↓CM | Inhibition of merozoite entry into the red cell, impairment of intracellular parasite growth and prevention of the erythrocyte lysis that occurs with parasite maturation, leading to release of merozoites into the blood stream. | [61,62] |
| Elliptocytosis | ↓SM | [63] | |
| Glycophorins A (GYP ABC) | ↓SM | [64,65] | |
| Blood Groups (ABO) |
↓SM | Reduced P. falciparum rosetting. | [66-68] |
| Haptoglobin (HP) |
↓SM | Oxidative damage to uninfected cells might be more marked in HP polymorphic individuals since HP proteins bind less efficiently to Hb, increasing premature destruction of erythrocytes and stimulating cytokine release by these circulating cells. | [69-71] |
| Nitric oxide synthase 2 (NOS2) |
↓SM | Increased NO production induces Th1 cytokines which activate macrophages and could thus be an anti-malarial resistance mechanism. | [72,73] |
| haem oxygenase I (HO-1) | ↓CM | Release of free haem in the blood stream. | [13,14] |