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Influence of ACE gene on differential response to sertraline versus fluoxetine in patients with major depression: a randomized controlled trial

Authors
  • Bahramali, Ehsan
  • Firouzabadi, Negar
  • Yavarian, Ilnaz
  • Shayesteh, Mohammad Reza Hooshangi
  • Erfani, Nasrallah
  • Shoushtari, Ali Alavi
  • Asadpour, Roja
Type
Published Article
Journal
European Journal of Clinical Pharmacology
Publisher
Springer-Verlag
Publication Date
Jun 05, 2016
Volume
72
Issue
9
Pages
1059–1064
Identifiers
DOI: 10.1007/s00228-016-2079-0
Source
Springer Nature
Keywords
License
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Abstract

BackgroundExtensive distribution of the different components of renin angiotensin system (RAS) in the brain, along with their roles in promoting anxiety, depression and brain inflammation, opposes RAS as a potential therapeutic target in major depression. Actions of angiotensin II, the main product of RAS, are reduced by antidepressants and this signifies the complex interplay of different mechanisms involved in response to therapy. Here, we hypothesized that genetic polymorphisms of RAS may affect the outcome of therapy in depressed patients.MethodsThe frequencies of variants of genes encoding for angiotensin-converting enzyme (ACE) insertion/deletion (I/D), rs4291 and rs4343 polymorphisms were determined in extracted DNAs of 200 newly diagnosed depressed patients. Patients were randomly divided into two groups, one treated with fluoxetine and the other treated with sertraline for 12 weeks. Responsive patients were determined by psychiatrist using Hamilton questionnaire and were compared with regard to their genetic variants.ResultsCarriers of the D allele and patients with DD genotype responded significantly better to sertraline than to fluoxetine (P = 0.0006, odds ratio (OR) = 3.0, 95 % confidence interval (CI) = 1.80–5.08; P = 0.006, OR = 3.7, 95 % CI = 1.66–8.29, respectively). Mutant genotypes (GG and TT) of rs4343 and rs4291 polymorphisms were also more frequent in patients responding to sertraline, though not achieving the significance level (P = 0.162 and P = 0.256, respectively).ConclusionThese findings suggest that special genetic variants of RAS may influence or be an indicator for better response to sertraline.

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