Impact of ACE 2 genetic variant on antidepressant efficacy of SSRIs.

BACKGROUNDS 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. ACE 2 catabolizes angiotensin II and produces angiotensin (1-7), an agonist of Mas receptor. Mice lacking the Mas receptor (angiotensin1-7 receptor) exhibit anxiety-like behaviors. 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). METHODS In a randomized control trial, two hundred newly diagnosed Iranian patients with major depressive disorder (MDD) completed 6 weeks of fluoxetine or sertraline treatment. Patients with a reduction of 50% or more in the Hamilton Rating Scale for Depression (HAM-D) score were considered responsive to treatment. G8790A polymorphism was determined in extracted DNAs using restriction fragment length polymerase chain reaction (PCR-RFLP) method. RESULTS The A allele as well as 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). CONCLUSIONS In conclusion our results confirm the role of G8790A in response to some SSRIs.