[Polymorphisms of the pfmdr1 gene in field samples of Plasmodium falciparum and their association with therapeutic response to antimalarial drugs and severe malaria in Colombia].
BACKGROUND
The pfmdr1 gene of Plasmodium falciparum has been described as a gene conferring resistance to several antimalarial drugs. In particular, polymorphisms on specific codons have been associated with resistance and treatment failure with cloroquine, amodiaquine and mefloquine. However, the role of these polymorphisms in treatment response to antimalarials remains unexplored in Colombia. Furthermore, the relationship of these polymorphisms to severe malaria is unknown.


OBJECTIVE
This work studied the association of the Asn 86Tyr and Asp1246Tyr pfmdr1 polymorphisms with response to cloroquine, amodiaquine and mefloquine treatment in three municipalities of Antioquia, and severe malaria cases from the municipality Tumaco.


METHODS
The polymorphisms were assessed by nucleic acid amplification followed by restriction length polymorphism analysis.


RESULTS
The wild-type codon Asn 86 was detected in 97% of the clinical samples from the treatment response study. No association was detected between this polymorphism and treatment failure to the three antimalarials administered. The 1246Tyr polymorphism was detected with a higher frequency in the samples from Antioquia 92% (130/141) than in those from Tumaco 22% (20/89). However, again, no association was found between the presence of a specific polymorphism and the presence of severe malaria in the municipality of Tumaco.


CONCLUSIONS
The 86Tyr and 1246Tyr polymorphisms of the pfmdr1 gene are not useful as predictors of treatment failure or severe malaria in the municipalities studied. In addition, we report for the first time, the presence of the mutant codon 86Tyr in field samples in South America.
Montoya
Paula
P
Grupo de Malaria, Sede de Investigación Universitaria, Universidad de Antioquia, Medellín, Colombia.
Tobón
Alberto
A
Blair
Silvia
S
Carmona
Jaime
J
Maestre
Amanda
A
D000655:Amodiaquine / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D002738:Chloroquine / Q000627:therapeutic use; D003105:Colombia; D018432:Drug Resistance, Multiple / Q000235:genetics*; D006801:Humans; D016778:Malaria, Falciparum / Q000145:classification / Q000188:drug therapy*; D015767:Mefloquine / Q000627:therapeutic use; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism
D000655:Amodiaquine; D000962:Antimalarials; D002738:Chloroquine; D015767:Mefloquine; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C513498:Mdr1 protein, Plasmodium falciparum