title: ACE I/D genotype-related increase in ACE plasma activity is a better predictor for schizophrenia diagnosis than the genotype alone.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Programa de Esquizofrenia (PROESQ) - Departamento de Psiquiatria, UNIFESP, São Paulo, Brazil.
authors.forename: Ary
authors.initials: A
authors.lastname: Gadelha
authors.affiliation: Departamento de Farmacologia, UNIFESP, São Paulo, Brazil.
authors.forename: Camila M
authors.initials: CM
authors.lastname: Yonamine
authors.affiliation: Departamento de Morfologia e Genética, UNIFESP, São Paulo, Brazil.
authors.forename: Vanessa K
authors.initials: VK
authors.lastname: Ota
authors.affiliation: Departamento de Biofísica, UNIFESP, São Paulo, Brazil.
authors.forename: Vitor
authors.initials: V
authors.lastname: Oliveira
authors.affiliation: Center of Mathematics, Computation and Cognition, Universidade Federal do ABC, Santo André, Brazil.
authors.forename: João Ricardo
authors.initials: JR
authors.lastname: Sato
authors.affiliation: Programa de Esquizofrenia (PROESQ) - Departamento de Psiquiatria, UNIFESP, São Paulo, Brazil; Departamento de Morfologia e Genética, UNIFESP, São Paulo, Brazil.
authors.forename: Sintia I
authors.initials: SI
authors.lastname: Belangero
authors.affiliation: Programa de Esquizofrenia (PROESQ) - Departamento de Psiquiatria, UNIFESP, São Paulo, Brazil.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Bressan
authors.affiliation: Departamento de Farmacologia, UNIFESP, São Paulo, Brazil. Electronic address: mhayashi@unifesp.br.
authors.forename: Mirian A F
authors.initials: MA
authors.lastname: Hayashi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D005838:Genotype; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D007703:Peptidyl-Dipeptidase A / Q000097:blood* / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012372:ROC Curve; D012559:Schizophrenia / Q000097:blood* / Q000235:genetics*; D055815:Young Adult
chemical_list: D007703:Peptidyl-Dipeptidase A
keywords: ACE; Enzyme activity; Genotype; Oligopeptidase; Schizophrenia