K13 Kelch Propeller Domain and mdr1 Sequence Polymorphism in Field Isolates From Northeast Region, India

Abstract

Emergence of artemisinin-resistant Plasmodium falciparum in Southeast Asia has made an intense warning to global malaria control programme since Southeast Asia is playing a key role in the evolution of drug resistant malaria parasites. Several polymorphisms in K13 gene have been designated with developing resistance either in vitro or in vivo . In this study, polymorphisms within K13 kelch propeller domain and Pf mdr1 gene were investigated in a total of 134 P. falciparum field isolates circulating in 3 states of Northeast region of India, namely, Assam, Arunachal Pradesh, and Tripura because information regarding this is limited from this region. Six polymorphisms were detected, out of which 2 were new. A481 V mutation was found in 4.5% of the total field isolates. A675 V and D702 N new mutations were present in 3.7% and 1.5% isolates, respectively. Synonymous polymorphism at codon 703 was highly observed (6.7%) than other polymorphisms. N86 Y allele in Pf mdr1 gene was also noticed in isolates that contained mutation in K13 propeller domain, but N86 wild-type allele was found comparatively higher in frequency within overall isolates. Moreover, both nucleotide and haplotype diversities in K13 gene were high in Arunachal Pradesh isolates than other 2 states. This is the first report from Northeast region of India with evidence of A675 V candidate mutation along with 2 other new mutations which pays attention for further molecular surveillance in this region to document detailed scenario of K13 polymorphism pattern corresponding to artemisinin resistance.