Impact of ACE2 genetic variant on antidepressant efficacy of SSRIs
- 4 October 2021
- journal article
- research article
- Published by Cambridge University Press (CUP) in Acta Neuropsychiatrica
- Vol. 34 (1), 30-36
- https://doi.org/10.1017/neu.2021.32
Abstract
Identification of a new axis of angiotensin-converting enzyme 2 (ACE2)/angiotensin (1–7)/Mas receptor, in the renin-angiotensin system (RAS), has opened a new insight regarding the role of RAS and angiotensin in higher brain functions. ACE2 catabolizes angiotensin II and produces angiotensin (1–7), an agonist of Mas receptor. Mice lacking the Mas receptor (angiotensin 1–7 receptor) exhibit anxiety-like behaviours. The present study was conducted to test the hypothesis of the involvement of ACE2 genetic variant (G8790A) on response to selective serotonin reuptake inhibitors (SSRIs). In a randomised control trial, 200 newly diagnosed Iranian patients with major depressive disorder completed 6 weeks of fluoxetine or sertraline treatment. Patients with a reduction of 50% or more in the Hamilton Rating Scale for Depression score were considered responsive to treatment. G8790A polymorphism was determined in extracted DNAs using restriction fragment length polymerase chain reaction method. Our results show that the A allele and AA and GA genotypes were significantly associated with better response to SSRIs (p = 0.008; OR = 3.4; 95% CI = 1.4–8.5 and p = 0.027; OR = 3.3, 95% CI = 1.2–9.2, respectively). Moreover, patients with GA and AA genotypes responded significantly better to sertraline (p = 0.0002; OR = 9.1; 95% CI = 2.4–33.7). The A allele was significantly associated with better response to sertraline (p = 0.0001; OR = 7.6; 95% CI = 2.5–23.3). In conclusion, our results confirm the role of G8790A in response to some SSRIs.Keywords
This publication has 59 references indexed in Scilit:
- The heterogeneity of the depressive syndrome: when numbers get seriousActa Psychiatrica Scandinavica, 2011
- A polymorphism in ACE2 is associated with a lower risk for fatal cardiovascular events in females: the MORGAM projectJournal of the Renin-Angiotensin-Aldosterone System, 2011
- Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: Therapeutic implicationsPsychoneuroendocrinology, 2011
- Angiotensin-converting enzyme (ACE) and ACE2 levels in the cerebrospinal fluid of patients with multiple sclerosisMultiple Sclerosis Journal, 2008
- Serotonin and depression: pathophysiological mechanism or marketing myth?Trends in Pharmacological Sciences, 2008
- Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin systemAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2007
- Polymorphisms in the angiotensin-converting enzyme gene are associated with unipolar depression, ACE activity and hypercortisolismMolecular Psychiatry, 2006
- Psychiatrist effects in the psychopharmacological treatment of depressionJournal of Affective Disorders, 2006
- Association of ACE, ACE2 and UTS2 Polymorphisms with Essential Hypertension in Han and Dongxiang Populations from North-western ChinaJournal of International Medical Research, 2006
- Brain angiotensin and anxiety-related behavior: The transgenic rat TGR(ASrAOGEN)680Brain Research, 2005