The Survival Strategies of Malaria Parasite in the Red Blood Cell and Host Cell Polymorphisms

Table 2

Red blood cell polymorphisms and mechanism of protection against severe malaria.

Name	Gene affected	Polymorphisms	Mechanism of protection	References
Invasion
Membrane proteins
Duffy negative	FY	GATA-1 motif	Duffy-negative RBCs fail to form an apical junction and prevents invasion of P. vivax and P. knowlesi	[3]
Glycophorin C deficiency	GYP C	Exon3 deletion	Protection against EBA-140-mediated invasion by P. falciparum parasites. Mechanism in common with other causes of ovalocytosis	[48, 49]
Band 3	SLC4A1	27 bp deletion	Resistance to invasion. Increased adhesion of P. falciparum-infected ovalocytes to CD36, thus reducing neurovascular binding of iRBCs in the brain	[48]
CR proteins	CR1	Sl2 or McCb	Reduced ability of P. falciparum—infected CR1—deficient red blood cells to form rosettes	[50]
ABO	ABO GlycosylT	Polymorphisms in exon 6 and 7	Loss of ABO Glycosyltransferase function results in the O blood group which prevents rosette formation	[51]
Replication within the RBC and/or elimination of iRBC
RBC enzymes
G6PD deficiency	G6PD	A376G/G202A [G6PD(A–)]	Early phagocytosis of iRBCs	[52]
PK deficiency	PKLR	*About 200 variants	Reduced rate of parasite replication within RBC and enhanced phagocytosis	[53]
Hemoglobinopathies
(i) Structural variants
HbS	HBB	β6: glutamate to valine	Increased sickling of parasitized erythrocytes leading to enhanced clearance by the spleen. Reduced erythrocyte invasion, early phagocytosis, and inhibited parasite growth under low oxygen tension in venous microvessels. Altered PfEMP-1 display and reduced cytoadherence of parasitized erythrocytes Enhancement of innate and acquired immunity	[1, 54]
HbC	HBB	β6: glutamate to lysine	Altered PfEMP-1 display and reduced cytoadherence of parasitized erythrocytes	[55]
HbE	HBB	β26: glutamate to lysine	Unidentified membrane abnormality renders resistant to invasion	[56]
(ii) Thalassemia
α-thalassemia	HBA1/HBA2	3.7-kb deletion	Reduced expression of CR1 reduces P. falciparum resetting and confers protection against severe malaria. Increased microerythrocyte count in homozygotes reduces the amount of hemoglobin lost for any given parasite density, thus protecting against severe anemia	[1]

^∗𝐏opulation distribution of variants are yet to be established.