Pharmacogenomic variants affecting efficacy and safety of medicines acting on central nervous system among Sri Lankans

Ensuring the efficacy and safety of medicines acting on the central nervous system (CNS) remains a challenge due to their complex pharmacokinetics and inter-individual variability in response. We describe the frequencies of pharmacogenomic variants affecting CNS drug metabolism in a Sri Lankan population. Pharmacogenomic data pertaining to genes of interest were obtained from the Pharmacogenomics Knowledgebase database. Pharmacokinetically relevant cytochrome P450 isoforms were selected. Their frequencies in Sri Lankans were obtained from an anonymized database derived from 690 participants, from the Human Genetics Unit, Faculty of Medicine, University of Colombo. Minor allele frequencies (MAFs) of these variants were calculated and compared with other populations. MAFs of <i>CYP2C19</i> rs4244285, <i>CYP2D6</i> rs16947, <i>CYP2D6</i> rs1058164, <i>CYP2D6</i> rs1135840, and <i>CYP2B6</i> rs3745274 were notably high at 40.9% (95%CI:38.3–43.5), 58.0% (95%CI:55.3–60.6), 43.8% (95%CI:41.1–46.4), 44.1% (95%CI:41.5–46.8), and 39.8% (95%CI:37.2–42.4), respectively. MAFs of <i>CYP2C9</i> rs72558189, <i>CYP2C19</i> rs4244285, <i>CYP2D6</i> rs77913725, <i>CYP2D6</i> rs1135828, and <i>CYP2B6</i> rs3745274 recorded the highest in Sri Lankans when compared to all other populations. A lower prevalence was noted in MAFs of <i>CYP2D6</i> rs1065852, <i>CYP2D6</i> rs16947, and <i>CYP2D6</i> rs28371706. Sri Lankans exhibit an increased susceptibility to adverse reactions with common antidepressants, antipsychotics, and analgesics and reduced efficacy to opioid analgesics. These findings highlight the need for population-specific pharmacogenomic guidelines.