Assessing the Roles of Molecular Markers of Antimalarial Drug Resistance and the Host Pharmacogenetics in Drug-Resistant Malaria

Table 1

Summary of current antimalarial drugs, their parasite molecular markers of resistance and human host pharmacogenetics.

Antimalarial drug	Molecular markers of resistance	Cytochrome P450 involved in the metabolism	Transporters involved in the transport of the antimalarial drugs
Quinine	pfmdr1 N86Y, Y184F, S1034C, N1042D, D1246Y [49]; pfmrp Y191, A437S [50]	CYP3A4, CYP3A5 [51, 52]; CYP2C9 [53]	MDR1 [19]; OCT1, OCT2 [47]
Halofantrine	Increased pfmdr1 copy number [54]	CYP3A4 and CYP3A5 [55]	Not available
Mefloquine	pfcrt K76T, A220S, Q271E, N326S, I356T, R371I; Increased pfmdr1 copy number, pfmdr1 N86Y [56, 57]	CYP3A4 [58]	MDR1, ABCG2 [59, 60]; ABCB1 [61]
Lumefantrine	pfmdr1 N86Y, Y184F, S1034C, N1042D, D1246Y [62]; Increased pfmdr1 copy number [63]	CYP3A4 and CYP3A5 [64]	ABCB1 [65].
Chloroquine	pfcrt K76T, K76N, K76I [66]; pfmdr1 N86Y [23]	CYP2C8, CYP3A4, and CYP3A5 [67]	The MDR1, MRP1, and MRP4 are involved in the transport of chloroquine [68]
Amodiaquine	pfmdr1 N86Y, Y184F, S1034C, N1042D, D1246Y, pfcrt K72T [69, 70]	CYP2C8, CYP1A1 and CYP1B1 [71]	Not available
Piperaquine	Increased pfpm2 and pfpm3 copy numbers [28, 72]	CYP3A4 and CYP2C8 [73]	Not available
Pyronaridine	pfmdr1 N86Y, Y184F, S1034C, N1042D, D1246Y, pfcrt K72T [74, 75]	CYP1A2, CYP2D6, and CYP3A4 [76]	Not available
Primaquine	Not available	CYP1A2, CYP3A4, and monoamine oxidase [77]	MRD1 and MRP1 [78]
Proguanil	pfdhfr S108N, N51I, and C59R [79]	CYP2C19 and CYP3A4 [21]	MATE1 and MAT2-K [80]
Pyrimethamine	pfdhfr S108N, N51I, C59R, 164 I164L, and A16V [4, 5]	Not available	Not available
Sulfadoxine	pfdhps S436F/A, A437G, K540E, A581G, and A613S/T [4, 5]	Not available	Not available
Artemisinin	pfk13 C580Y, R539T, I543T, F446L, N458Y, P547L, R56IH, Y493H [81], pfatp6 A623E, S769N [82]	CYP2B6, CYP3A4, and CYP2A6 [83]	P-glycoproteins [84]
Atovaquone	pfcytb Y268S/C/N, M133I, L144S, G280D [85, 86]	Not available	Not available