Single-Nucleotide Polymorphism and Copy Number Variation of the Multidrug Resistance-1 Locus of Plasmodium vivax: Local and Global Patterns

Author(s)

del Carmen, Rosa ^[1] ; Vargas-Rodriguez, Miluska ^[1] ; Bastos, Melissa da Silva ^[1] ; Menezes, Maria Jose ^[1] ; Orjuela-Sanchez, Pamela ^[2] ; Ferreira, Marcelo U. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, BR-05508900 Sao Paulo - Brazil

^[2] La Jolla Bioengn Inst, San Diego, CA - USA

• Document type: Journal article
• Source: American Journal of Tropical Medicine and Hygiene; v. 87, n. 5, p. 813-821, NOV 2012.
• Web of Science Citations: 19

Abstract

Emerging resistance to chloroquine (CQ) poses a major challenge for Plasmodium vivax malaria control, and nucleotide substitutions and copy number variation in the P. vivax multidrug resistance 1 (pvmdr-1) locus, which encodes a digestive vacuole membrane transporter, may modulate this phenotype. We describe patterns of genetic variation in pvmdr-1 alleles from Acre and Amazonas in northwestern Brazil, and compare then with those reported in other malaria-endemic regions. The pvmdr-1 mutation Y976F, which is associated with CQ resistance in Southeast Asia and Oceania, remains rare in northwestern Brazil (1.8%) and its prevalence mirrors that of CO resistance worldwide. Gene amplification of pvmdr-1, which is associated with mefloquine resistance but increased susceptibility to CO, remains relatively rare in northwestern Brazil (0.9%) and globally (< 4%), but became common (> 10%) in Tak Province, Thailand, possibly because of drug-mediated selection. The global database we have assembled provides a baseline for further studies of genetic variation in pvmdr-1 and drug resistance in P. vivax malaria. (AU)

• FAPESP's process: 10/51835-7 - Chloroquine resistance in Plasmodium vivax: phenotypic and molecular evaluation in Brazilian Western Amazon
• Grantee: Marcelo Urbano Ferreira
• Support Opportunities: Regular Research Grants