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

Negar Firouzabadi, Roja Asadpour, Kamiar Zomorrodian

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] 

Major Depressive Disorder; Fluoxetine; Genetic Polymorphism; Pharmacogenetics

Ballenger JC, Davidson JR, Lecrubier Y, Nutt DJ, Goldberg D, Magruder KM et al. Consensus statement on the primary care management of depression from the International Consensus Group on Depression and Anxiety. J Clin Psychiatry 1999;60(suppl 7):54-61.

Demyttenaere K, Bruffaerts R, Posada-Villa J, Gasquet I, Kovess V, Lepine J et al. Prevalence, severity, and unmet need for treatment of mental disorders in the World Health Organization World Mental Health Surveys. JAMA. 2004;291(21):2581-90.


Sullivan PF, Neale MC, Kendler KSJAJoP. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry 2000;157(10):1552-62.


Milak MS, Parsey RV, Keilp J, Oquendo MA, Malone KM, Mann JJJAoGP. Neuroanatomic correlates of psychopathologic components of major depressive disorder. JAMA Psychiatry. 2005;62(4):397-408.


Hirschfeld RJTJocp. History and evolution of the monoamine hypothesis of depression. J Clin Psychiatry. 2000; 61, 4-6.

Elhwuegi ASJPiN-P, Psychiatry B. Central monoamines and their role in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28(3):435-51.


Yang-Feng TL, Xue F, Zhong W, Cotecchia S, Frielle T, Caron MG et al. Chromosomal organization of adrenergic receptor genes. PNAS. 1990;87(4):1516-20.

PMid:2154750 PMCid:PMC53506

Delgado PL, Moreno FAJTJocp. Role of norepinephrine in depression. J Clin Psychiatry. 2000; 61, 5-12.

Amsterdam JD, Newberg AB, Newman CF, Shults J, Wintering N, Soeller IJJoN. Change over time in brain serotonin transporter binding in major depression: effects of therapy measured with [123I]-ADAM SPECT. J Neuroimaging. 2013;23(4):469-76.

PMid:23751132 PMCid:PMC4592779

Cai X, Kallarackal AJ, Kvarta MD, Goluskin S, Gaylor K, Bailey AM et al. Local potentiation of excitatory synapses by serotonin and its alteration in rodent models of depression. Nat. Neurosci. 2013;16(4):464.

PMid:23502536 PMCid:PMC3609911

Ahlquist RPJAJoP-LC. A study of the adrenotropic receptors. Am J Physiol. 1948;153(3):586-600.


Gautam N, Downes G, Yan K, Kisselev OJCs. The G-protein βγ complex. Cell Signal. 1998;10(7):447-55.

Whalen EJ, Foster MW, Matsumoto A, Ozawa K, Violin JD, Que LG et al. Regulation of β-adrenergic receptor signaling by S-nitrosylation of G-protein-coupled receptor kinase 2. Cell. 2007;129(3):511-22.


Burcescu I, Wigg K, Gomez L, King N, Vetro A, Kiss E et al. Association study of the adrenergic receptors and childhood-onset mood disorders in Hungarian families. Am J Med Genet. 2006;141(3):227-33.


Mason DA, Moore JD, Green SA, Liggett SBJJoBC. A gain-of-function polymorphism in a G-protein coupling domain of the human β1-adrenergic receptor. J Biol Chem. 1999;274(18):12670-4.


Zill P, Baghai TC, Engel R, Zwanzger P, Schüle C, Minov C et al. Beta-1-adrenergic receptor gene in major depression: Influence on antidepressant treatment response. Am J Med Genet B. 2003;120(1):85-9.


Rush AJ, Trivedi MH, Wisniewski SR, Stewart JW, Nierenberg AA, Thase ME et al. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. NEJM. 2006;354(12):1231-42.


Association AP. Diagnostic criteria from dsM-iV-tr. American Psychiatric Pub; 2000.

Hamilton M. A rating scale for depression. J. Neurol. Neurosurg. Psychiatry. 1960;23(1):56.

PMid:14399272 PMCid:PMC495331

Miller S, Dykes D, Polesky HJNar. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16(3):1215.

PMid:3344216 PMCid:PMC334765

Moriyama A, Nishizawa D, Kasai S, Hasegawa J, Fukuda K-i, Nagashima M et al. Association between genetic polymorphisms of the β1-adrenergic receptor and sensitivity to pain and fentanyl in patients undergoing painful cosmetic surgery. J Pharmacol Sci. 2013;121(1):48-57.


Auerbach RP, Mortier P, Bruffaerts R, Alonso J, Benjet C, Cuijpers P et al. WHO World Mental Health Surveys International College Student Project: prevalence and distribution of mental disorders. J Abnorm Psychol. 2018;127(7):623.

PMid:30211576 PMCid:PMC6193834

Machado M, Iskedjian M, Ruiz I, Einarson TRJCmr, opinion. Remission, dropouts, and adverse drug reaction rates in major depressive disorder: a meta-analysis of head-to-head trials. Curr Med. 2006;22(9):1825-37.


Schosser A, Kasper SJIcp. The role of pharmacogenetics in the treatment of depression and anxiety disorders. Int Clin Psychopharmacol. 2009;24(6):277-88.


Serretti A, Artioli P, Quartesan RJP, genomics. Pharmacogenetics in the treatment of depression: pharmacodynamic studies. Pharmacogenet Genomics. 2005;15(2):61-7.


Taylor MJTpj. Pharmacogenetics of the human beta-adrenergic receptors. Pharmacogenomics J. 2007;7(1):29.


Crissman AM, Makhay MM, O'Donnell JMJP. Discriminative stimulus effects of centrally administered isoproterenol in rats: mediation by beta-1 adrenergic receptors. Psychopharmacology. 2001;154(1):70-5.


Crowley JJ, Lipsky RH, Lucki I, Berrettini WHJPg. Variation in the genes encoding vesicular monoamine transporter 2 and beta-1 adrenergic receptor and antidepressant treatment outcome. Psychiatr Genet. 2008;18(5):248-51.


Firouzabadi N, Raeesi R, Zomorrodian K, Bahramali E, Yavarian IJJoP, Sciences P. Beta adrenoceptor polymorphism and clinical response to sertraline in major depressive patients. J Pharm Pharm Sci. 2017;20:1-7.



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