title: Role of Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes on in vitro chloroquine resistance in isolates of Plasmodium falciparum from Thailand.
abstract: Resistance to chloroquine is a public health problem worldwide. Polymorphisms of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes have been linked to chloroquine resistance. Although the K76T mutation in the pfcrt gene has been shown to be a key determinant in chloroquine resistance, evidence suggests that the pfmdr1 gene could modulate the level of chloroquine resistance. However, few studies of field isolates could identify the interactive role of these two genes in chloroquine resistance. Thus, we evaluated the influence of pfcrt and pfmdr1 polymorphisms on in vitro chloroquine sensitivity in 89 adapted isolates of P. falciparum from Thailand. We found that 87 of 89 isolates contained the CVIET haplotype of the pfcrt gene. Two additional mutations in the pfcrt gene were identified, i.e., K6Q and H97L. For the pfmdr1 polymorphisms, the 184F allele was common in the parasites isolated along the Thailand-Cambodia border, and those isolated along the Thailand-Myanmar border contained higher copy numbers. Our results indicate that the additional mutations, in particular H97L in the pfcrt gene and Y184F in the pfmdr1 gene and its copy number, influence the level of chloroquine resistance.
authors: Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand. chavachol@hotmail.com
authors: Chavachol
authors: C
authors: Setthaudom
authors: Peerapan
authors: P
authors: Tan-ariya
authors: Naruemon
authors: N
authors: Sitthichot
authors: Rommanee
authors: R
authors: Khositnithikul
authors: Nantana
authors: N
authors: Suwandittakul
authors: Saovanee
authors: S
authors: Leelayoova
authors: Mathirut
authors: M
authors: Mungthin
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001483:Base Sequence; D002738:Chloroquine / Q000494:pharmacology*; D017931:DNA Primers; D026901:Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism*; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics / Q000502:physiology*; D013785:Thailand
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000962:Antimalarials; D017931:DNA Primers; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine