Genetic variation in ACE A2350G: association with reduction in fasting blood glucose after fluoxetine therapy in depressed patients

Various studies have shown that genetic factors contribute substantially to the development and progression of diabetes. Renin-angiotensin system has long been proven to have a major role in cardiovascular physiology and pathology. Its major product Angiotensin II (Ang II) with pro oxidant properties has shown to predict the future risk of diabetes. Fluoxetine, a drug of choice in management of depression, was observed to reduce fasting blood sugar (FBS). In the present study, six common polymorphisms of genes encoding for RAS components were determined in DNAs extracted from venous blood of 100newly diagnosed depressed individuals taking 12 weeks of fluoxetine. Blood samples were collected prior and after the period of treatment in order to measure FBS. Our results indicate that carriers of GG genotype of ACE A2350G showed significantly lower FBS levels after fluoxetine treatment (P=0.043). On the other hand haplotype analysis designate a significant association between DTG carriers of ACE I/D, A-240T and A2350G (P=0.001) and reduced FBS levels. In conclusion, this study supports the hypothesis that RAS genetic variations affect blood glucose after a course of treatment in Iranian population with depressio

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 &amp; 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.</p