HTR1A-RS6295 polymorphism and selective serotonin reuptake inhibitor treatment outcome in major depressive disorder patients
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1
Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia
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2
Putra Malaysia University, Malaysia
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3
Institute of Bioscience, University Putra Malaysia, Malaysia
Background
Production of serotonin is influenced by serotonin-1A receptor (5HTR1A). RS6295-HTR1A is a promoter region polymorphism in the HTR1A gene, which is characterised by cytosine(C) substitution with guanine (G), which modulates serotonergic neurotransmission. The current study was aimed at determining the association between HTR1A-RS6295 gene polymorphism with SSRI treatment outcome.
Methodology
Consecutive sampling was adopted for recruiting consenting multiethnic Malaysian patients in four tertiary hospitals, namely Hospital Serdang, Hospital Kajang, Hospital Putrajaya and Hospital Kuala Lumpur. Montgomery Asberg Depression Rating Scale-self Rated (MADRS-S) was used in determining efficacy of SSRI following 6 weeks of treatment. Adverse effects (AEs) were assessed using Patient Rated Inventory of Side Effect (PRISE) at the 6th week of treatment. Statistical evaluation of association between genotypes of HTR1A-RS6295, obtained through sequencing of PCR products, with phenotypes of efficacy and AEs, before and after adjustment with covariates was done.
Results
There were 314 patients, 211 (67%) were females and 154 (49%) were Malays. In this study, 73.4%, 70.7% and 71.7% of the patients were observed to have a specific-clinical, clinical and partial-early response to treatment. Adverse effects (AEs) reported included; insomnia (34.2%) and headache (30.9%) among others. There were numerous significant associations between genotypes of HTR1A-RS6295 and AE of SSRI, However, on assessing the percentage of inflation of odds ratio, only the association between dizziness and CG genotype had an acceptable level of confounding (≤10%).
Conclusion
There were numerous association findings for AE treatment outcomes with genotypes of HTR1A-RS6295 in the current study. However, only the association of the CG genotype with dizziness was not marred by any confounding effect and thus was an accurate representation of true association. Therefore, this genotype holds a great potential for clinical utilisation in the near future for predicting dizziness.
Acknowledgements
Thanks to Putra grant for supporting the project and thanks to Bayero Universsity Kano for sponsoring the PhD. studies of Dr. IBM
Keywords:
pharmacogenetic,
SSRI (selective serotonergic reuptake inhibitors),
adverse effect,
efficacy,
HTR1A
Conference:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019.
Presentation Type:
Oral Presentation
Topic:
Miscellaneous
Citation:
Badamasi
IM,
Stanslas
J,
Lye
M,
Shaari
K and
Ibrahim
N
(2019). HTR1A-RS6295 polymorphism and selective serotonin reuptake inhibitor treatment outcome in major depressive disorder patients.
Front. Pharmacol.
Conference Abstract:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”.
doi: 10.3389/conf.fphar.2018.63.00006
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Received:
24 Sep 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Dr. Ibrahim M Badamasi, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia, badamasiibrahimmohammed@gmail.com