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Impact of ACE2 genetic variant on antidepressant efficacy of SSRIs

Published online by Cambridge University Press:  04 October 2021

Negar Firouzabadi Open the ORCID record for Negar Firouzabadi [Opens in a new window] ,
Parisa Farshadfar ,
Maral Haghnegahdar ,
Ali Alavi-Shoushtari  and
Vahid Ghanbarinejad
Negar Firouzabadi*
Affiliation:
Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Parisa Farshadfar
Affiliation:
Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Maral Haghnegahdar
Affiliation:
Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
Ali Alavi-Shoushtari
Affiliation:
Department of Psychiatry, UCLA-Kern, Bakersfield, CA, USA Department of Psychiatry, School of Medicine, Hafez Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
Vahid Ghanbarinejad
Affiliation:
Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
*
Author for correspondence: Negar Firouzabadi, Emails: [email protected], [email protected]
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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

major depressive disordergenetic polymorphismsingle nucleotide polymorphismfluoxetinesertraline
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 34 , Issue 1 , February 2022 , pp. 30 - 36
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Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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