Lack of association between putative transporter gene polymorphisms in Plasmodium falciparum and chloroquine resistance in imported malaria isolates from Africa.
BACKGROUND
Plasmodium falciparum drug resistance represents a major health problem in malaria endemic countries. The mechanisms of resistance are not fully elucidated. Recently, an association between putative transporter gene polymorphisms and in vitro response to chloroquine (CQ) and quinine has been reported in culture-adapted, cloned isolates from various geographical origins. However, this was not confirmed in another study performed on isolates from a defined region in Thailand.


METHODS
This study tried to find an association between putative transporters gene polymorphisms with in vitro response to CQ and pfcrt genotype in isolates originating from various African countries. To avoid biases of parasites adaptation in culture, fresh isolates obtained from symptomatic, malaria-infected travellers returning from Africa to France were used. Monoclonal isolates included in the study were selected using a msp-2 fragment analysis method. In vitro susceptibility to CQ, single nucleotide polymorphisms and microsatellite polymorphisms in pfcrt, pfmdr1 and six putative transporter genes were established in 27 isolates and three reference strains.


RESULTS
Polymorphism of pfcrt at positions 76 and 220 showed a significant association with in vitro chloroquine resistance (P < .02 and P < .05 respectively). Polymorphism of pfmdr1 at position 86 showed an equally significant association with in vitro chloroquine response (P < .05). No association was found between SNPs or microsatellite polymorphisms of putative transporter genes and in vitro CQR or pfcrt genotype in imported malaria isolates from Africa.


CONCLUSIONS
The previously described association between putative transporter gene polymorphisms and in vitro response to chloroquine (CQ) was not confirmed in the present study.
Centre National de Référence pour la Chimiosensibilité du Paludisme, APHP, Hôpital Bichat-Claude Bernard, Paris, France. sandrine.cojean@wanadoo.fr
Sandrine
S
Cojean
Alain
A
Noël
Dimitri
D
Garnier
Véronique
V
Hubert
Jacques
J
Le Bras
Rémy
R
Durand
D000349:Africa; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics*; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics*; D005602:France; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D015800:Protozoan Proteins / Q000235:genetics*; D014195:Travel
D000962:Antimalarials; D002352:Carrier Proteins; D015800:Protozoan Proteins; D002738:Chloroquine