title: Detection of point mutation in Plasmodium falciparum ATPase6 gene associated with artemisinin resistance from Assam and Arunachal Pradesh.
abstract: OBJECTIVE
  Resistance against partner drugs of artemisinin has been reported from different parts of India. The study aims to find out the single nucleotide polymorphisms in Plasmodium falciparum ATPase6 gene associated with artemisinin resistance.
  
  
  METHODS
  Blood samples were collected from 141 patients with P. falciparum monoinfection in malaria endemic zones of Assam and Arunachal Pradesh. A 645 bp portion of PfATPase6 gene was amplified and sequenced to determine the frequency of mutations associated with resistance to artemisinin.
  
  
  RESULTS
  Mutations at codon S769N, which have been proposed to confer artemisinin resistance, were not detected in our study samples. Instead of that a novel non-synonymous mutation (C-T) at 1847 bp position resulting in serine to phenylalanine alteration at codon S616F was detected from the P. falciparum field isolates in Changlang district of Arunachal Pradesh, whereas no mutation was detected in any of the analyzed samples in Assam indicating that wild type PfATPase6 genotype was found circulating in this region. Overall, based on the mutational pattern, two haplotypes of PfATPase6 gene were observed during the study, the wild type and mutant S616F allele. The overall haplotype diversity (Hd) was found to be: 0.069 and nucleotide diversity (per site Pi): 0.00012. Highest haplotype diversity was recorded in Changlang district of Arunachal Pradesh having Hd value of 0.33333 along with single polymorphic site and nucleotide diversity (Pi): 0.00060. A pair-wise fixation index (FST) value of 0.16667 indicates great genetic differentiation within the parasite population of Changlang district with the population of Karbi Anglong, Chirang, Tinsukia, Sivasagar, Jorhat, NC Hills, Lakhimpur, Golaghat and Dibrugarh districts of Assam and Lohit district of Arunachal Pradesh.
  
  
  CONCLUSIONS
  A better understanding of the distribution of antimalarial drug resistance with malaria parasite may provide insight into some of the epidemiological determinants of the increasing case burden.
authors.affiliation: Entomology and Filariasis Division, Regional Medical Research Centre (ICMR), North East Region, Dibrugarh, India.
authors.forename: Jitendra
authors.initials: J
authors.lastname: Sharma
authors.forename: Prafulla
authors.initials: P
authors.lastname: Dutta
authors.forename: S A
authors.initials: SA
authors.lastname: Khan
authors.forename: Monika
authors.initials: M
authors.lastname: Soni
authors.forename: Jagadish
authors.initials: J
authors.lastname: Mahanta
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007194:India; D016778:Malaria, Falciparum / Q000469:parasitology; D008297:Male; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D016054:DNA, Protozoan; C031327:artemisinin; D025261:Mitochondrial Proton-Translocating ATPases