Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/18103
Title: Single Nucleotide Polymorphisms in Cellular Drug Transporters Are Associated with Intolerance to Antiretroviral Therapy in Brazilian HIV-1 Positive Individuals
Authors: Arruda, Mônica Barcellos
Campagnari, Francine
Almeida, Tailah Bernardo de
Fernandez, José Carlos Couto
Tanuri, Amilcar
Cardoso, Cynthia Chester
Affilliation: Universidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Virologia Molecular. Rio de Janeiro, RJ, Brasil.
Deoxi Biotecnologia. Araçatuba, SP, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Virologia Molecular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Virologia Molecular. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biologia. Departamento de Virologia Molecular. Rio de Janeiro, RJ, Brasil.
Abstract: Adverse reactions are the main cause of treatment discontinuation among HIV+ individuals. Genes related to drug absorption, distribution, metabolism and excretion (ADME) influence drug bioavailability and treatment response. We have investigated the association between single nucleotide polymorphisms (SNPs) in 29 ADME genes and intolerance to therapy in a case-control study including 764 individuals. Results showed that 15 SNPs were associated with intolerance to nucleoside and 11 to non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs), and 8 to protease inhibitors (PIs) containing regimens under alpha = 0.05. After Bonferroni adjustment, two associations remained statistically significant. SNP rs2712816, at SLCO2B1 was associated to intolerance to NRTIs (ORGA/AA = 2.37; p = 0.0001), while rs4148396, at ABCC2, conferred risk of intolerance to PIs containing regimens (ORCT/TT = 2.64; p = 0.00009). Accordingly, haplotypes carrying rs2712816A and rs4148396T alleles were also associated to risk of intolerance to NRTIs and PIs, respectively. Our data reinforce the role of drug transporters in response to HIV therapy and may contribute to a future development of personalized therapies.
Keywords: HIV-1
Antiretroviral Therapy
Single Nucleotide Polymorphisms
Brazil
Positive Individuals
keywords: HIV-1
Brasil
Terapia antiretroviral
Polimorfismos de nucleotídeo único
Pacientes
Issue Date: 2016
Publisher: Public Library of Science
Citation: ARRUDA, Mônica Barcellos; et al. Single Nucleotide Polymorphismsin Cellular Drug Transporters Are Associatedwith Intolerance to Antiretroviral Therapy in Brazilian HIV-1 Positive Individuals. PLoS ONE, v.11, n.9, e0163170, 11p, Sept. 2016.
DOI: 10.1371/journal.pone.0163170
ISSN: 1932-6203
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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