Pharmacogenomic variants affecting efficacy and safety of medicines acting on central nervous system among Sri Lankans.
| Title: | Pharmacogenomic variants affecting efficacy and safety of medicines acting on central nervous system among Sri Lankans. |
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| Authors: | Ranasinghe P; Department of Pharmacology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.; Peiris C; Department of Pharmacology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.; Jeyapragasam H; Department of Pharmacology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.; Sirisena ND; Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.; Hendalage DPB; Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka.; Dissanayake VHW; Department of Anatomy, Genetics and Biomedical Informatics, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka. |
| Source: | Pharmacogenomics [Pharmacogenomics] 2025 Jul-Aug; Vol. 26 (10-12), pp. 339-347. Date of Electronic Publication: 2025 Sep 13. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Taylor & Francis Country of Publication: England NLM ID: 100897350 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1744-8042 (Electronic) Linking ISSN: 14622416 NLM ISO Abbreviation: Pharmacogenomics Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2024- : [Milton Park, Oxfordshire] : Taylor & Francis; Original Publication: London : Ashley Publications |
| MeSH Terms: | Pharmacogenomic Variants*/genetics ; Central Nervous System Agents*/adverse effects ; Central Nervous System Agents*/therapeutic use ; Central Nervous System Agents*/pharmacokinetics ; Central Nervous System*/drug effects; Sri Lanka/epidemiology ; Cytochrome P-450 CYP2D6/genetics ; Gene Frequency/genetics ; Pharmacogenetics/methods ; Cytochrome P-450 CYP2C19/genetics ; Polymorphism, Single Nucleotide/genetics ; Humans ; Male ; Female ; Adult |
| Abstract: | Background: 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.; Methods: 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.; Results: MAFs of CYP2C19 rs4244285, CYP2D6 rs16947, CYP2D6 rs1058164, CYP2D6 rs1135840, and CYP2B6 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 CYP2C9 rs72558189, CYP2C19 rs4244285, CYP2D6 rs77913725, CYP2D6 rs1135828, and CYP2B6 rs3745274 recorded the highest in Sri Lankans when compared to all other populations. A lower prevalence was noted in MAFs of CYP2D6 rs1065852, CYP2D6 rs16947, and CYP2D6 rs28371706.; Conclusion: 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. |
| Contributed Indexing: | Keywords: CNS medicines; CYP2B6; CYP2C19; CYP2C9; CYP2D6; Pharmacogenomics; South Asia; Sri Lanka |
| Substance Nomenclature: | EC 1.14.14.1 (Cytochrome P-450 CYP2D6); EC 1.14.14.1 (Cytochrome P-450 CYP2C19); 0 (Central Nervous System Agents); EC 1.14.14.1 (CYP2C19 protein, human) |
| Entry Date(s): | Date Created: 20250913 Date Completed: 20251009 Latest Revision: 20251105 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12582073 |
| DOI: | 10.1080/14622416.2025.2558498 |
| PMID: | 40944712 |
| Database: | MEDLINE |
Journal Article