Lack of association of indoleamine 2,3-dioxygenase polymorphisms with interferon-alpha-related depression in hepatitis C

Lack of association of indoleamine 2,3-dioxygenase polymorphisms with interferon-alpha-related depression in hepatitis C

Author Almeida, Amanda Cristina Galvão Oliveira de Autor UNIFESP Google Scholar
Quarantini, Lucas de Castro Autor UNIFESP Google Scholar
Sampaio, Aline Santos Autor UNIFESP Google Scholar
Lyra, André Castro Google Scholar
Parise, Carmen Livia Autor UNIFESP Google Scholar
Paraná, Raymundo Google Scholar
Oliveira, Irismar Reis de Google Scholar
Koenen, Karestan C Google Scholar
Miranda-Scippa, Ângela Marisa de Aquino Autor UNIFESP Google Scholar
Guindalini, Camila Autor UNIFESP Google Scholar
Institution Universidade Federal da Bahia (UFBA)
Universidade Federal de São Paulo (UNIFESP)
Harvard Univ
Abstract Background: Major depression is a frequent adverse effect of interferon-alpha (IFN-alpha) therapy. Although the indoleamine 2,3-dioxygenase (IDO) enzyme seems to be involved in the pathophysiology of IFN-alpha-induced depression, no pharmacogenetic study has investigated Whether variation in the IDO gene modifies vulnerability to this adverse effect.Methods: A cross-sectional study assessing 277 hepatitis C patients recruited in two specialized outpatient clinics of Brazil. They were interviewed with the Mini International Neuropsychiatric Interview (MINI) approximately 1 month after the end of IFN-alpha plus ribavirin therapy. Genomic DNA of individuals was extracted from venous blood. Three IDO single-nucleotide polymorphisms (SNPs) were genotyped (rs3824259; rs10089084 and rs35099072).Results: MINI indicated that 21.3% of the sample met criteria for a major depressive episode during the course of IFN-alpha therapy. No association with the diagnosis of a major depressive episode during the course of IFN-alpha therapy was observed genotype or allele-wise (p > 0.05). Current major depression and/or current anxiety disorder was significantly associated with IFN-alpha-related depression (p < 0.005). However, gender, age, route of infection, result of the antiviral treatment, past history of substance use disorders, depression or any other psychiatric disorder showed no association with IFN-a-related depression (p > 0.05).Conclusions: Our results suggest no influence of the variants in the IDO gene and the diagnosis of interferon-alpha-related depression in the Brazilian population. Interferon-alpha-related depression may impose persistent psychopathology on at least 15% of the depressed patients even 2 years after antiviral therapy termination. the cross-sectional design is a limitation of our study, predisposing memory bias. Prospective pharmacogenetic studies are warranted to continue investigation of the impact of IDO polymorphisms on the development of IFN-alpha-induced depression. (C) 2011 Elsevier Inc. All rights reserved.
Keywords Interferon-alpha
Major depressive disorder
Hepatitis C
Genetic polymorphism
Substance-related disorders
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number CNPq: 471592/2008-0
CNPq: 142262/2008-0
Date 2011-10-01
Published in Brain Behavior and Immunity. San Diego: Academic Press Inc Elsevier Science, v. 25, n. 7, p. 1491-1497, 2011.
ISSN 0889-1591 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1491-1497
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000295554300027

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