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Response to sertraline is influenced by GNβ3 gene G-350A variant in patients with major depressive disorder

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

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.

Method

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.

Results

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).

Conclusion

The results suggest that G-350A variant of GNβ3 plays a foremost part as a predictor of response to antidepressant treatment.

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Acknowledgements

This manuscript is dedicated to Professor Habib Firouzabadi, on the occasion of his 75th birthday.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Dena Firouzabadi

  2. Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Negar Firouzabadi, Kiana Kalani & Elham Shirazi Tehrani

  3. Basic Sciences in Infectious Diseases Research Center, Shiraz, Iran

    Kamyar Zomorrodian

  4. Department of Medical Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Kamyar Zomorrodian

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  1. Dena Firouzabadi
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  2. Negar Firouzabadi
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Contributions

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.

Corresponding author

Correspondence to Negar Firouzabadi.

Ethics declarations

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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Firouzabadi, D., Firouzabadi, N., Kalani, K. et al. Response to sertraline is influenced by GNβ3 gene G-350A variant in patients with major depressive disorder. Eur J Clin Pharmacol 75, 189–194 (2019). https://doi.org/10.1007/s00228-018-2577-3

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  • DOI: https://doi.org/10.1007/s00228-018-2577-3

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