Response to sertraline is influenced by GNβ3 gene G-350A variant in patients with major depressive disorder
Heterotrimeric guanine nucleotide-binding proteins (G proteins) are a major group of human genome membrane protein receptors. Genetic variation in the β3 subunit (GNβ3) associated with gene splicing and increased activity is associated with major depressive disorder (MDD). However, the effect of G-350A GNβ3 genetic polymorphism and therapeutic outcome of selective serotonin reuptake inhibitors (SSRIs) in MDD has not yet been studied.
One hundred newly diagnosed MDD patients were treated with sertraline for 6 weeks. The severity of depressive symptoms was weekly assessed by Hamilton Rating Scale for Depression (HRSD). A 50% decrease in HRSD was defined as response to treatment. GNβ3 polymorphisms (G-350A, A657T) were determined in each individual using a PCR-RFLP technique.
Our results suggested that subjects with GG genotype of G-350A responded 5.9-folds more to sertraline compared to carriers of other variants (P = 0.004, OR = 5.9; 95% CI = 1.66–21.99). In addition, carriers of the G allele responded 1.9-folds more to sertraline than carriers of the A allele (P = 0.032, OR = 1.92; 95% CI = 1.05–3.65). However, no association was observed between A657T variants and response to sertraline (P = 0.920, OR = 0.9; 95% CI = 0.31–2.69).
The results suggest that G-350A variant of GNβ3 plays a foremost part as a predictor of response to antidepressant treatment.
KeywordsPharmacogenetics Polymorphism Sertraline Depression
This manuscript is dedicated to Professor Habib Firouzabadi, on the occasion of his 75th birthday.
Contributions of authors
Negar Firouzabadi: Design of the work, analysis, and interpretation of data for the work, drafting the work, and final approval of the manuscript.
Dena Firouzabadi: Analysis and interpretation of data for the work, revising the manuscript critically for important intellectual content, and final approval of the manuscript.
Kiana Kalani: Substantial contributions to the conception of the project, drafting the manuscript, and final approval of the manuscript.
Kamiar Zomorodian: Design of the work, analysis, and interpretation of data for the work, drafting the work, and final approval of the manuscript.
Elham Shirazi Tehrani: Analysis and interpretation of data for the work, revising the manuscript critically for important intellectual content, and final approval of the manuscript.
Compliance with ethical standards
This study was approved by the local committee for ethics of medical experiments on human subjects of Shiraz University of Medical Sciences and carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki) and Uniform Requirements for manuscripts submitted to biomedical journals.
Conflict of interest
The authors declare that they have no conflict of interest.
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