Association study of the beta-adrenergic receptor genetic variant Gly389Arg and fluoxetine response in major depression

Abstract

Background: Pharmacogenetics has proven role in the treatment of different illnesses. Patients with special genotypes may achieve a better response to a specific drug. On the other hand, genetic parameters markedly contribute to the development of major depressive disorder (MDD). The significance of adrenergic system compartments in cognition and behavior, and their role in etiology of depression denote that adrenergic receptors beta gene polymorphism(s) might also have an association with drug response. Thus this study aims to evaluate the association between β1AR gene polymorphisms, G1165C, Arg389Gly and response to fluoxetine in MDD patients. Materials and Methods: Among different antidepressants, we focused on fluoxetine as it is prescribed frequently in MDD and belongs to one of the most efficient antidepressant categories with minimum side effects. MDD was diagnosed at study entry using DSM-IV criteria. One hundred and one new MDD patients were treated with fluoxetine for a period of 6 weeks. A 50% decrease in Hamilton Rating Scale for Depression (HRSD) was considered as response to treatment. Genotyping of G1165C polymorphism was performed by PCR-RFLP method. Results: Results of the study indicated no significant relationship between β1AR polymorphism and the patient’s response to fluoxetine neither at genotypic nor allelic level (P=0.568). Conclusion: Our study did not support the hypothesis of involvement of β1AR Arg389Gly polymorphism and response to fluoxetine in MDD patients. [GMJ.2020;9:e1781]

The Role of Beta-Adrenergic Receptors in Depression and Resilience

“…A clinical study discerned the influence of the G1165C polymorphism in the beta-1 adrenoceptor gene on individual differences in response to sertraline, and it was found that CC genotype-carrying individuals responded five times more to sertraline compared to other variants and that the C allele carriers responded three times more to sertraline than patients with the G allele [ 63 ]. Interestingly, the antidepressant-promoting effect of polymorphism in the beta-1 adrenoceptor gene was not observed in patients who received repeated treatment with fluoxetine, one of the most frequently prescribed antidepressants [ 64 ]. Moreover, the antidepressant-induced down-regulation of CNS beta-1 adrenoceptors in rodents was in a time course that paralleled the onset of antidepressant action in patients with MDD [ 65 ].…”