title: DNA sequence polymorphisms of the pfmdr1 gene and association of mutations with the pfcrt gene in Indian Plasmodium falciparum isolates.
abstract: Mutations in the Plasmodium falciparum multidrug resistance (pfmdr1) gene are known to provide compensatory fitness benefits to the chloroquine (CQ)-resistant malaria parasites and are often associated with specific mutations in the P. falciparum CQ resistant transporter (pfcrt) gene. Prevalence of the specific mutations in these two genes across different malaria endemic regions was mostly studies. However, reports on mutations in the pfmdr1 gene and their genetic associations with mutations in the pfcrt gene in Indian P. falciparum field isolates are scarce. We have sequenced a 560 bp region of pfmdr1 coding sequence in 64 P. falciparum isolates collected from different malaria endemic populations in India. Twenty out of these 64 isolates were laboratory cultured with known in vitro CQ sensitiveness (10 sensitive and 10 resistant). Three low frequency mutations (two non-synonymous and one synonymous) in the pfmdr1 gene were segregating in Indian isolates in addition to the predominant Y₈₆ and Y₁₈₄ ones, with high haplotype and nucleotide diversity in the field isolates in comparison to the cultured ones. No statistically significant genetic association between the mutations in the pfmdr1 and pfcrt gene could be detected; almost all observed associations were intragenic in nature. The results on the genetic diversity of the pfmdr1 gene were discussed in term of evolutionary perspectives in Indian P. falciparum, with possible future potential of gaining further insights on this gene in view of evolving malaria parasites resistant to artemisinin partner drugs.
authors.affiliation: Evolutionary Genomics and Bioinformatics Laboratory, Division of Genomics and Bioinformatics, National Institute of Malaria Research, Sector 8, Dwarka, New Delhi 110077, India.
authors.forename: Kshipra
authors.initials: K
authors.lastname: Chauhan
authors.affiliation: Department of Biotechnology, Kumaun University, Nainital 263001, Uttarakhand, India.
authors.forename: Veena
authors.initials: V
authors.lastname: Pande
authors.affiliation: Evolutionary Genomics and Bioinformatics Laboratory, Division of Genomics and Bioinformatics, National Institute of Malaria Research, Sector 8, Dwarka, New Delhi 110077, India. Electronic address: aparup@mrcindia.org.
authors.forename: Aparup
authors.initials: A
authors.lastname: Das
mesh_terms: D005787:Gene Frequency; D005838:Genotype; D005843:Geography; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D015810:Linkage Disequilibrium; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology*; D026901:Membrane Transport Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009154:Mutation; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum
keywords: India; Pfcrt; Plasmodium falciparum; Single Nucleotide Polymorphisms (SNPs); pfmdr1