title: Analysis of genetic diversity in the chloroquine-resistant gene Pfcrt in field Plasmodium falciparum isolates from five regions of the southern Cameroon.
abstract: Understanding the population genetics of genes which shape resistance to antimalarial drugs can help in devising novel control strategies. The high spread of the resistant strains of the malaria parasite Plasmodium falciparum pose a greater challenge than before to the control programs across the world. Specific mutations in the P. falciparum chloroquine resistant transporter gene "Pfcrt" have been associated with resistance to not only chloroquine, but also to amodiaquine, one of the artemisinin partners used in Cameroon for the treatment of uncomplicated malaria. We here present data on genetic variation at the Single Nucleotide Polymorphisms (SNPs) level in the Pfcrt gene in five distinct geographical settings of the Southern-Cameroon (the most malaria endemic part), i.e. Ebolowa, Yaounde, Bertoua, Douala and Kye-ossi (a city bordering Cameroon and two others African countries). Two novel mutations, hitherto unreported (in Cameroon) were found in the Pfcrt gene and variable genetic diversity was observed across the populations. High linkage disequilibrium was found between few SNPs including one of the novel mutations suggesting a synergistic work for conferring/maintaining a higher level of resistance. The inference of evolutionary pattern of this gene in Cameroon based on the genetic diversity data depicts a signature of Darwinian positive natural selection on these loci. Observation of novel mutations might traduce new variants in chloroquine/or amodiaquine resistance (proposal awaiting an experimental verification) and signal of positive selection can be the result of drug pressure exerted by misuse of chloroquine (though officially banned from the country) and/or amodiaquine. Our findings thus, provide a baseline understanding of the evolution of a malaria drug resistant gene in Cameroon and suggest a successful establishment of chloroquine-resistant strains which requires urgent attention of the malaria control program in Cameroon.
authors.affiliation: Evolutionary Genomics and Bioinformatics Laboratory, Division of Genomics and Bioinformatics, National Institute of Malaria Research, Dwarka Sector 8, New Delhi-110077, India.
authors.forename: Huguette Gaelle
authors.initials: HG
authors.lastname: Ngassa Mbenda
authors.affiliation: Evolutionary Genomics and Bioinformatics Laboratory, Division of Genomics and Bioinformatics, National Institute of Malaria Research, Dwarka Sector 8, New Delhi-110077, India. Electronic address: aparupdas.crme@gmail.com.
authors.forename: Aparup
authors.initials: A
authors.lastname: Das
mesh_terms: D000962:Antimalarials / Q000494:pharmacology; D002163:Cameroon / Q000453:epidemiology; D002738:Chloroquine / Q000494:pharmacology*; D004351:Drug Resistance; D014644:Genetic Variation; D005838:Genotype; D015810:Linkage Disequilibrium; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology*; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: D000962:Antimalarials; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine
keywords: Cameroon; Chloroquine-resistance; P. falciparum-malaria; Pfcrt; Single nucleotide polymorphism