Pharmacogenetic assessment of 5‐HT1A‐rs6295 (C1019G) and 5‐HT2A‐rs6311 (G1438A) Receptor gene polymorphisms in SSRI treatment outcome among Malays in malaysia
Authors: Badamasi Ibrahim Mohammed , Stanslas Johnson Mohammed , Sann Lye Munn , Ibrahim Normala , Shaari Khozirah , Ling Michael KH. 
Published: June 2021

SSRI medications had steadily manifested unacceptable level of low efficacy and higher adverse effect over time. There are several pharmacogentic studies that revealed an association between serotonergic genes such as rs6295‐HT1A and rs6311‐HT2A with treatment outcome among MDD patents. Nevertheless, there are other studies that failed to replicate these association findings. The mechanisms through which these polymorphisms influence treatment outcome are not entirely known. Functional studies had revealed that both C>G change of rs6295 and G>A change for rs6311 were associated with increased activity and expression of the receptor protein encoded by the genes. At present, there are no objective methods for determining whether a patient would experience a favourable or unfavourable treatment outcome. The current study aims to determine the association between 5‐HT1A‐rs6295 (C1019G) and 5‐HT2A‐rs6311 (G1438A) gene polymorphisms with six weeks SSRI treatment outcome among Malays diagnosed with first episode MDD. Recruitment with blood sampling of consenting MDD patient by consecutive sampling technique was done. Montgomery asberg Depression Rating Scale‐self Rated (MADRS‐S) instrument was used in determining the severity of depression before and after 6 weeks of treatment. Different paradigms of treatment response, which points to different cut‐off values in changes for MADRS score; such as clinical response (≥50%), specific clinical response (≥55%), partial early response (≥25%) and remission response (≥85%) were assessed. Adverse effects (AE) were assessed using patient‐rated inventory of side effect (PRISE) at the end of the study. Adjusted logistic regression evaluation for association findings were carried out. There were 128 patients with completed data on adverse effect and 120 patients with response to treatment data. The treatment response paradigms reported in this study were clinical response (82 (68%)), specific clinical response (68 (68%)), partial‐early response (85 (70.8%)) and remission response (38 (31.4%)) respectively. SSRI treatment induced adverse effect was observed in 109 (85.2%) patients. Heightened odds for both clinical response (OR=47.619, CI=4.484–500.000, p=0.001) and specific clinical response (OR=408.29 (CI=9.86–16900.69; p=0.001) were observed for rs6295‐G/G when assessed using a co‐dominant model. Rs6311‐A/A (HT2A), was associated with an increased odd for specific clinical response especially when it was evaluated using a dominant model (OR= 58.598, CI=4.857–706.921, p=0.001). There was an increase in odds for dry skin among carriers of rs6295‐C/G (p=0.048, OR=7.936, CI=1.020–62.500) when it was assessed in a co‐dominant model. Patients carrying rs6311‐A allele were observed to be at increased odd for nausea/vomiting (p=0.024, OR=10.526, CI=1.369–83.333) when assessed through a recessive model.ConclusionRs6295‐G and RS6311‐A predict different paradigm of treatment responses, dry skin A.E and nausea/vomiting A.E among Malay patients diagnosed with FEMDD.Support or Funding InformationI am a postgraduate student at Universti Putra Malaysia and am fully sponsoring my self for the conference tripThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.