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PLoS One ; 12(3): e0174647, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28358908

RESUMO

Heroin dependent patients have a high incidence of HIV infection. In contrast to the gene expression method, we developed a systemic correlation analysis method built upon the results of pharmacogenomics study in a methadone maintenance treatment (MMT) cohort consisting of 344 Taiwanese heroin dependent patients. We identified genetic variants and their encoding proteins that may be involved with HIV infection and MMT treatment outcome. Cadherin 2 (CDH2) genetic determinants were identified through the genome-wide pharmacogenomic study. We found significant correlations among HIV infection status, plasma levels of CDH2, cytokine IL-7, ADAM10, and the treatment responses to methadone. Two single nucleotide polymorphisms located within CDH2 gene showed associations with blood pressure and plasma CDH2 concentration. Plasma concentration of CDH2 showed correlations with the level of cytokine IL-7, status of HIV infection, and urine morphine test result. Plasma level of IL-7 was correlated with corrected QT interval (QTc) and gooseflesh skin withdrawal symptom score, while level of ADAM10 was correlated with plasma concentrations of vitamin D metabolite, nicotine metabolite, and R-methadone. The results suggest a novel network involving HIV infection and methadone treatment outcome.


Assuntos
Antígenos CD/genética , Caderinas/genética , Infecções por HIV/tratamento farmacológico , Dependência de Heroína/tratamento farmacológico , Metadona/farmacocinética , Proteína ADAM10/sangue , Adulto , Secretases da Proteína Precursora do Amiloide/sangue , Antígenos CD/sangue , Caderinas/sangue , Feminino , Infecções por HIV/sangue , Infecções por HIV/complicações , Infecções por HIV/genética , Heroína/efeitos adversos , Dependência de Heroína/sangue , Dependência de Heroína/complicações , Dependência de Heroína/genética , Humanos , Interleucina-7/sangue , Masculino , Proteínas de Membrana/sangue , Metadona/uso terapêutico , Morfina/efeitos adversos , Farmacogenética , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento , Vitamina D/metabolismo
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