Open AccessGenome-wide association analysis identifies genetic loci associated with resistance to multiple antimalarials in Plasmodium falciparum from China-Myanmar border
Author(s) -
Zenglei Wang,
Mynthia Cabrera,
Jingyun Yang,
Lili Yuan,
Bhavna Gupta,
Xiaoying Liang,
Karen Kemirembe,
Sony Shrestha,
Awtum Brashear,
Xiaolian Li,
Stephen F. Porcella,
Jun Miao,
Zhaoqing Yang,
Xin-zhuan Su,
Liwang Cui
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep33891
Subject(s) - plasmodium falciparum , locus (genetics) , biology , dihydroartemisinin , malaria , drug resistance , genetics , piperaquine , artemisinin , genome wide association study , single nucleotide polymorphism , chloroquine , genome , gene , genotype , immunology
Drug resistance has emerged as one of the greatest challenges facing malaria control. The recent emergence of resistance to artemisinin (ART) and its partner drugs in ART-based combination therapies (ACT) is threatening the efficacy of this front-line regimen for treating Plasmodium falciparum parasites. Thus, an understanding of the molecular mechanisms that underlie the resistance to ART and the partner drugs has become a high priority for resistance containment and malaria management. Using genome-wide association studies, we investigated the associations of genome-wide single nucleotide polymorphisms with in vitro sensitivities to 10 commonly used antimalarial drugs in 94 P. falciparum isolates from the China-Myanmar border area, a region with the longest history of ART usage. We identified several loci associated with various drugs, including those containing pfcrt and pfdhfr . Of particular interest is a locus on chromosome 10 containing the autophagy-related protein 18 (ATG18 ) associated with decreased sensitivities to dihydroartemisinin, artemether and piperaquine – an ACT partner drug in this area. ATG18 is a phosphatidylinositol-3-phosphate binding protein essential for autophagy and recently identified as a potential ART target. Further investigations on the ATG18 and genes at the chromosome 10 locus may provide an important lead for a connection between ART resistance and autophagy.