Investigating the Impact of Inherited Genetic Variations on Antidepressant Drug Response Using ARMS Genotyping

Abstract

Major Depressive Disorder (MDD) is a severe mental health condition affecting millions of people worldwide that can impact daily functioning and is caused by the regulation of serotonin. Selective serotonin reuptake inhibitors (SSRIs) are the primary treatment for MDD. CYP2D6 encodes an enzyme involved in drug metabolism of SSRIs antidepressants. This study aimed to evaluate pharmacogenetics' ability to improve SSRI treatment outcomes by genotyping CYP2D6 SNPs associated with poor SSRI metabolism. This was done using the Amplification Refractory Mutation System (ARMS), where primers were designed to produce specific amplicons for different alleles of the targeted SNPs. Three SNPs were examined with random HRC-2 DNA samples. The results showed that the primers for SNP rs35742686 and SNP rs5030655 worked well after optimization, while SNP rs3892097 primers were deemed unreliable for further use. A tri-ARMS protocol with three primers for each SNP was successfully combined for SNPs rs35742686 and rs5030655. However, multiplexing both SNPs in one ARMS reaction proved difficult to interpret due to close fragment sizes. Genotyping CYP2D6 SNPs provided insights into the metabolism of SSRIs. In conclusion, the findings from the CYP2D6 gene analysis have significant implications for personalised medicine and drug therapy. As research in pharmacogenomics continues to advance, it is essential to address the complexities of genetic diversity and the translation of genomic data into clinical practice. Further studies with larger sample sizes and diverse populations will be essential for refining our understanding of drug metabolism variability and improving therapeutic outcomes.