Multiple mechanisms such as genetic and epigenetic variations within a key gene may play a role in malarial susceptibility and response to
anti-malarial drugs in the population. ABCB1 is one of the well-studied
membrane transporter genes that code for the
P-glycoprotein (an efflux
protein) and whose effect on
malaria disease predisposition and susceptibility to drugs remains to be understood. We studied the association of single
nucleotide variations in human ABCB1 that influences its function in subjects with uncomplicated and complicated
malaria caused by Plasmodium falciparum (Pf). Global DNA methylation and ABCB1
DNA promoter methylation levels were performed along with transcriptional response and
protein expression in subjects with
malaria and healthy controls. The rs2032582 locus was significantly associated with complicated and combined
malaria groups when compared to controls (p < 0.05). Significant DNA methylation difference was noticed between case and control (p < 0.05). In addition, global DNA methylation levels of the host
DNA were inversely proportional to
parasitemia in individuals with Pf
infection. Our study also revealed the correlation between ABCB1
DNA promoter methylation with rs1128503 and rs2032582 polymorphisms in
malaria and was related to increased expression of
ABCB1 protein levels in complicated
malaria group (p < 0.05) when compared to uncomplicated
malaria and control groups. The study provides evidence for multiple mechanisms that may regulate the role of host ABCB1 function to mediate aetiology of
malaria susceptibility, prognosis and drug response. These may have clinical implications and therapeutic application for various malarial conditions.