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Am. J. Trop. Med. Hyg., 77(6), 2007, pp. 1034-1038
Copyright © 2007 by The American Society of Tropical Medicine and Hygiene

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SHORT REPORT


Polymorphisms in the pfcrt and pfmdr1 Genes of Plasmodium falciparum and in Vitro Susceptibility to Amodiaquine and Desethylamodiaquine

Diego F. Echeverry*, Gabrielle Holmgren, Claribel Murillo, Juan C. Higuita, Anders Björkman, Jose P. Gil, AND Lyda Osorio
International Center for Medical Research and Training (CIDEIM), Cali, Colombia; Malaria Research Unit, Department of Infectious Diseases, Division of Medicine, Karolinska Institute, Stockholm, Sweden

 

ABSTRACT

The potential role of polymorphisms in the pfcrt and pfmdr1 genes and in vitro susceptibility to amodiaquine and desethylamodiaquine were explored in 15 chloroquine-resistant Colombian Plasmodium falciparum isolates. Single nucleotide polymorphisms in the pfcrt gene, including a newly reported mutation (S334N), were seen in isolates with decreased susceptibility to amodiaquine and desethylamodiaquine. The lowest susceptibility found to amodiaquine was observed in an isolate carrying a pfcrt and pfmdr1 Dd2-like haplotype, whereas a pfcrt haplotype related to the 7G8 Brazilian strain was found in a Colombian isolate with the lowest susceptibility to desethylamodiaquine. This exploratory study suggests that polymorphisms in the pfcrt and pfmdr1 genes play a role in amodiaquine and desethylamodiaquine resistance and warrants further study.

Received March 21, 2007. Accepted for publication September 5, 2007.

Financial support: This work was supported by an anonymous Swiss foundation.

* Address correspondence to Diego F. Echeverry, International Center for Medical Research and Training (CIDEIM), Avenida 1 Norte 3–03, Cali, Valle, Colombia. E-mail: difereg{at}cideim.org.co

Authors’ addresses: Diego F. Echeverry, International Center for Medical Research and Training (CIDEIM), Avenida 1 Norte 3–03, Cali, Colombia, Telephone: 572–6682164, Fax: 572–6672989. Gabrielle Holmgren, Malaria Research Lab, M9/02, Karolinska Hospital, Stockholm 17176, Sweden. Claribel Murillo, International Center for Medical Research and Training (CIDEIM), Avenida 1 Norte 3–03, Cali, Valle, Colombia, Telephone: 572–6682164, Fax: 572–6672989. Juan C. Higuita, Universidad Nacional de Colombia, Manizales, Departamento de Ingeniería Química. Manizales, Colombia. Anders Bjorkman, Malaria Research Lab, M9/02, Karolinska Hospital, Stockholm 17176, Sweden. Jose P. Gil, Malaria Research Lab, M9/02, Karolinska Hospital, Stockholm 17176, Sweden. Lyda Osorio, International Center for Medical Research and Training (CIDEIM), Avenida 1 Norte 3–03, Cali, Colombia, Telephone: 572–6682164, Fax: 572–6672989.






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