Table 1.
Summary of current molecular markers associated with antimalarial drug resistance.
| Genes (accession numbers) | Chromosome location | Common codon mutations linked to drug resistance in the various genes | Antimalarial drugs/Drug class |
|---|---|---|---|
| Pfcrt (PF3D7_0709000)§ | 7 | Mutations (76T) | Chloroquine and Amodiaquine |
| Pfmdr1 (PF3D7_0523000)# | 5 | Mutations (86Y, 124F, 1042D, 1246Y) | Chloroquine, Amodiaquine, Lumefantrine, Mefloquine |
| Mutations (184F) | Mefloquine, artesunate | ||
| Increased copy number | Mefloquine | ||
| Pfdhfr (PF3D7_0417200)α | 4 | Mutations (51I, 59R, S108N, 164L) | Pyrimethamine, Cycloguanil |
| Pfdhps (PF3D7_0810800)¥ | 8 | Mutations (436A, 437G, 540E, 581G, 613S/T) | Sulfonamide, Sulfadoxine, Sulfone, Dapsone |
| Pfmrp1 (PF3D7_0112200)∗ | 1 | Mutations (191H, 437S) | Chloroquine, quinine |
| Pfcytb (mal_mito_3)∗∗ | Mitochondrial genome | Mutations (268N/S/C) | Atovaquone |
| Pfnhe-1 (PF3D7_1303500)& | 13 | Repeat polymorphism (DNNND repeat motif in microsatellite ms470 region) | Quinine |
| PfATPase4 (PF3D7_1211900)¶ | 12 | Mutations (398F, 990R, 211T, 415D, 917L) | Spiroindolones, Pyrazoles, Dihydroisoquinolones |
| PfATPase6 (PF3D7_0106300)¶¶ | 1 | Mutations (263E, 431K, 623E, 769N) | Artemisinin and its derivatives |
| Pfpm 2 (PF3D7_1408000)‡ | 14 | Increased copy number | Piperaquine |
| Pfk13 (PF3D7_1343700)‡‡ | 13 | Mutations (446I, 458Y, 476I, 493H, 539T, 543T, 553L, 561H, 580Y) | ART and its derivatives |
ART: Artemisinin; Pf: Plasmodium falciparum; Pfatpase6: Pf Ca2+-ATPase; Pfcrt: Pf chloroquine resistance transporter; Pfdhfr: Pf dihydrofolate reductase; Pfcytb: Pf cytochrome B; Pfdhps: Pf dihydropteroate synthase; Pfk13: Pf Kelch gene; Pfmdr1: Pf multidrug resistance protein 1 (the protein is called Pgh1, P-glycoprotein homolog 1); Pfmrp1: Pf multidrug resistance protein 1; Pfnhe-1: Pf sodium–hydrogen exchanger; Pfpm: Pf Plasmepsin.
Information was based on Peterson et al., 1988α; Triglia et al. (1997)¥; Korsinczky et al., 2000∗∗; Singh Sidhu et al., 2002§; Mu et al., 2003∗; Jambou et al. (2005)¶¶; Sidhu et al., 2005#; Ferdig et al., 2004&; Henry et al., 2009&; Ariey et al., 2014‡‡; Chilongola et al. (2015)¶; Spillmarn and Kirk (2015)¶; Menard and Dondorp (2017); Bopp et al. (2018)‡.
Mutations proposed for PfATPase6 gene 6 are still not validated for drug resistance while the link between increased number in Pfpm2 gene and resistance to piperaquine is still controversial.