ACE genetic variability and response to fluoxetine: lack of association in depressed patients

Evidences suggest that besides the neurotransmitters contributing to the development of depression, renin-angiotensin system (RAS) may also have a substantial role. Certain polymorphisms of RAS are associated with over activity of RAS & depression. Considering that antidepressants reduce the actions of angiotensin II, the main product of RAS, this may come into mind that genetic polymorphisms of the mentioned system may affect the outcome of therapy in depressed patients.In the present study, 100 newly diagnosed depressed patients, according to DSM-IV criteria, were treated with 20 mg of fluoxetine for 8-12 weeks. Patients were categorized into responsive and non-responsive groups according to 50% reduction in symptoms. Genotype frequencies of angiotensin-converting enzyme (ACE) gene [ACE (I/D, A-240T and A2350G)] were then determined in DNAs extracted from venous blood of the patients using polymerase chain reaction–restriction fragment length polymorphism (PCR– RFLP) and PCR.Results indicate that polymorphisms studied and their haplotypes were not associated with better response to fluoxetine. However, a strong association between age and treatment in depressed Iranian patients was observed (P=0.001).In conclusion, unlike previous reports, this study does not support the hypothesis of special genotypes of RAS contributing to a better response to antidepressants in depressed patients.