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

被引:21
作者
Gadelha, Ary [1 ]
Yonamine, Camila M. [2 ]
Ota, Vanessa K. [3 ]
Oliveira, Vitor [4 ]
Sato, Joao Ricardo [5 ]
Belangero, Sintia I. [1 ,3 ]
Bressan, Rodrigo A. [1 ]
Hayashi, Mirian A. F. [2 ]
机构
[1] Univ Fed Sao Paulo, Dept Psiquiatria, Programa Esquizofrenia PROESQ, Sao Paulo, Brazil
[2] Univ Fed Sao Paulo, Dept Farmacol, Sao Paulo, Brazil
[3] Univ Fed Sao Paulo, Dept Morfol & Genet, Sao Paulo, Brazil
[4] Univ Fed Sao Paulo, Dept Biofis, Sao Paulo, Brazil
[5] Univ Fed ABC, Ctr Math Computat & Cognit, Santo Andre, Brazil
基金
巴西圣保罗研究基金会;
关键词
Schizophrenia; ACE; Enzyme activity; Oligopeptidase; Genotype; ANGIOTENSIN-CONVERTING ENZYME; GENE INSERTION/DELETION POLYMORPHISM; CEREBROSPINAL-FLUID; DELETION POLYMORPHISM; KININASE-II; ASSOCIATION; INHIBITION; RECEPTOR;
D O I
10.1016/j.schres.2015.01.044
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
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.
引用
收藏
页码:109 / 114
页数:6
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