ACE I/D genotype-related increase in ACE plasma activity is a better predictor for schizophrenia diagnosis than the genotype alone

ACE I/D genotype-related increase in ACE plasma activity is a better predictor for schizophrenia diagnosis than the genotype alone

Author Gadelha, Ary Autor UNIFESP Google Scholar
Yonamine, Camila M. Autor UNIFESP Google Scholar
Ota, Vanessa K. Autor UNIFESP Google Scholar
Oliveira, Vitor Autor UNIFESP Google Scholar
Sato, Joao Ricardo Google Scholar
Belangero, Sintia I. Autor UNIFESP Google Scholar
Bressan, Rodrigo A. Autor UNIFESP Google Scholar
Hayashi, Mirian A. F. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade Federal do ABC (UFABC)
Abstract Background: Angiotensin-I converting enzyme (ACE) is a key component of the renin-angiotensin system(RAS). Although the several contradictory data, ACE has been associated with schizophrenia (SCZ) pathophysiology. Here the ACE activity of SCZ patients and healthy controls (HCs), and its possible correlations with the ACE polymorphism genotype and symptomatic dimensions, was investigated.Methodology: ACE activity of 86 SCZ patients and 100 HCs paired by age, gender and educational level was measured, using the FRET peptide substrate and the specific inhibitor lisinopril. the ACE insertion/deletion (I/D) genotypes were assessed by the restriction fragment length polymorphism (RFLP) technique.Results: Significantly higher ACE activity was observed in SCZ patients compared to HCs (t=-5.09; p < 0.001). the area under the receiver operating characteristic (ROC) curve was 0.701. Mean ACE activity levels were higher for the D-allele carriers (F = 5.570; p = 0.005), but no significant difference was found among SCZ patients and HCs for genotypes frequencies (Chi-squared = 2.08; df = 2; p = 0.35). Interestingly, we found that the difference between the measured ACE activity for each SCZ patient and the expected average mean value for each respective genotype group (for control subjects) was a better predictor of SCZ than the ACE dichotomized values (high/low) or ACE I/D.Conclusion: Our results suggest that higher levels of ACE activity are associated with SCZ with stronger impact when the genetic background of each individual is considered. This may explain the heterogeneity of the results on ACE previously reported. (C) 2015 Elsevier B.V. All rights reserved.
Keywords Schizophrenia
Enzyme activity
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2012/08941-6
Date 2015-05-01
Published in Schizophrenia Research. Amsterdam: Elsevier B.V., v. 164, n. 1-3, p. 109-114, 2015.
ISSN 0920-9964 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 109-114
Access rights Closed access
Type Article
Web of Science ID WOS:000353337100016

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