Journal article
Variation in Human Cytochrome P-450 drug-metabolism genes: A gateway to the understanding of plasmodium vivax relapses
ACR Silvino, GL Costa, FCF De Araújo, DB Ascher, DEV Pires, CJF Fontes, LH Carvalho, CFA De Brito, TN Sousa
Plos One | PUBLIC LIBRARY SCIENCE | Published : 2016
Open access
Abstract
Although Plasmodium vivax relapses are classically associated with hypnozoite activation, it has been proposed that a proportion of these cases are due to primaquine (PQ) treatment failure caused by polymorphisms in cytochrome P-450 2D6 (CYP2D6). Here, we present evidence that CYP2D6 polymorphisms are implicated in PQ failure, which was reinforced by findings in genetically similar parasites, and may explain a number of vivax relapses. Using a computational approach, these polymorphisms were predicted to affect the activity of CYP2D6 through changes in the structural stability that could lead to disruption of the PQ-enzyme interactions. Furthermore, because PQ is co-Administered with chloroq..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This work was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) (455353/2014-0), CNPq/PROEP and Fundacao de Amparo a Pesquisa do estado de Minas Gerais (FAPEMIG). CJFF, LHC and CFAB are CNPq fellows. DBA is supported by an NHMRC CJ Martin Fellowship (APP1072476). DBA and DEVP are supported by a Newton Fund RCUK-CONFAP Grant awarded by The Medical Research Council and FAPEMIG. DEVP receives support from Centro de Pesquisas Rene Rachou (CPqRR/FIOCRUZ). ACRS and GLC receive graduate and postgraduate scholarships support from CNPq. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.