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

• Published in: The pharmacogenomics journal 2021-08, Vol.21 (4), p.498-509
• Main Authors: Badamasi, Ibrahim Mohammed, Lye, Munn Sann, Ibrahim, Normala, Abdul Razaq, Nurul Asyikin, Ling, King Hwa, Stanslas, Johnson
• Format: Article
• Language: English
• Subjects: 45; 45/22; 45/23; 45/77; 631/208/205; 692/53/2423; Adolescent; Adult; Antidepressants; Biomedical and Life Sciences; Biomedicine; Clinical outcomes; Constipation; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - genetics; Diarrhea; Drug therapy; Female; Gene Expression; Gene polymorphism; Genetic aspects; Genetic polymorphisms; Genotype; Genotype & phenotype; Human Genetics; Humans; Major depressive disorder; Malaysia; Male; Mental depression; Middle Aged; Nausea; Oncology; Patient outcomes; Patients; Pharmacology, Experimental; Pharmacotherapy; Phenotypes; Polymorphism; Polymorphism, Single Nucleotide - genetics; Psychopharmacology; Receptors; Selective Serotonin Reuptake Inhibitors - therapeutic use; Serotonin; Serotonin uptake inhibitors; Sweating; Vomiting; Young Adult
• ISSN: 1470-269X; 1473-1150
• DOI: 10.1038/s41397-021-00228-6

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.