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Serotonergic receptor gene polymorphism and response to selective serotonin reuptake inhibitors in ethnic Malay patients with first episode of major depressive disorder

The Pharmacogenomics Journal volume 21, pages 498–509 (2021)Cite this article

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Abstract

The polymorphisms of the 5HTR1A and 5HTR2A receptor genes (rs6295C/G and rs6311G/A) have been evaluated for association with SSRI treatment outcome in various populations with different results. The present study was carried out to determine the association between genotypes of HTR1A-rs6295 and HTR2A-rs6311 with SSRI treatment outcome among the ethnic Malay patients diagnosed with first-episode major depressive disorder (MDD). The patients were recruited from four tertiary hospitals in the Klang Valley region of Malaysia. Predefined efficacy phenotypes based on 25% (partial early response) and 50% (clinical efficacy response) reduction in Montgomery Asberg Depression Rating Scale-self Rated score (MADRS-S) were adopted for assessment of treatment efficacy in this study. Self-reporting for adverse effects (AE) was documented using the Patient Rated Inventory of Side Effect (PRISE) after treatment with SSRI for up to 6 weeks. Adjusted binary logistic regression between genotypes of the polymorphism obtained using sequencing technique with the treatment outcome phenotypes was performed. The 142 patients recruited were made up of 96 females (67.6%) and 46 males (32.4%). Clinical efficacy and Partial early response phenotypes were not significantly associated with genotypes of HTR1A and HTR2A polymorphism. The GG genotype of HTR2A polymorphism has decreased odds for dizziness (CNS) and increased odds for poor concentration. The GA genotype increases the odd for excessive sweating, diarrhoea, constipation and blurred vision. The CC genotype of HTR1A-rs6295 decreases the odd for nausea/vomiting and increases the odd for anxiety. Thus, some genotypes of HTR1A and HTR2A polymorphism were associated with SSRI treatment outcomes in ethnic Malay MDD patients.

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Acknowledgements

Universiti Putra Malaysia is thanked for funding this project via the Group Initiative Putra Grant (GP/IPB/2013/9415702). We thank the Director-General of Health Malaysia for his permission to publish this study (NMRR-14-688-19696). We thank Bayero University Kano (Nigeria) for sponsoring the Ph.D fellowship of IBM. We also thank the patients and staff of the hospitals involved, as well as Dr. Azizul Awaluddin, Dr. Sharifah Suziah Syed Mokhtar, Dr. Mazni Mat Junus, Dr. Elinda Tunan, Dr. Su Peng Loh, Prof Rozita Rosli, Dr. Yin Yee Tey, Dr. Vaidehi Ulanganathan, Ms. Aldoghachi Asraa Faris Abdulridha, Mr. Khairul Aiman Bin Lokman, Ms. Siti Zubaidah Redzuan, and all those who have assisted in one way or another.

Funding

The research was funded by Putra grant GP-IPB/2013/9415702. IBM’s Ph.D was sponsored by Bayero University Kano through the TETFund scholarship and University fellowship award.

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  1. Ibrahim Mohammed Badamasi

    Present address: Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, Bayero University, Kano, Nigeria

Authors and Affiliations

  1. Pharmacotherapeutics Unit, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia

    Ibrahim Mohammed Badamasi & Johnson Stanslas

  2. Department of Community Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia

    Munn Sann Lye

  3. Department of Psychiatry, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia

    Normala Ibrahim & Nurul Asyikin Abdul Razaq

  4. Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia

    King Hwa Ling

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  1. Ibrahim Mohammed Badamasi
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Correspondence to Johnson Stanslas.

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Badamasi, I.M., Lye, M.S., Ibrahim, N. et al. Serotonergic receptor gene polymorphism and response to selective serotonin reuptake inhibitors in ethnic Malay patients with first episode of major depressive disorder. Pharmacogenomics J 21, 498–509 (2021). https://doi.org/10.1038/s41397-021-00228-6

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