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Author: search.filters.author.Perera, NSubject: search.filters.subject.Pharmacogenomics

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    PublicationOpen Access
    In Silico Analysis of the Diversity of DPYD Gene Variants Aff ecti ng Fluoropyrimidine Toxicity: A Comparison of South Asians with Other World Populati ons
    (Faculty of Humanities and Sciences, SLIIT, 2024-12-04) Perera, N; Weerasinghe, M; Kasturiarachchi, J; Ranasinghe, P
    Fluoropyrimidine (FP) chemotherapy drug is uti lized to treat colon, head, neck and breast cancers. Apart from its eff ecti veness, toxicity is a limitati on. DPD (dihydropyrimidine dehydrogenase) enzyme, which aids in the FP metabolism is produced by the highly polymorphic DPYD gene. Mutati ons in the DPYD gene cause the defi ciency or non-functi onality of the DPD enzyme which varies among diff erent populati ons. This research aimed to compare allele frequencies of common DPYD gene variants of South Asians (SAS) such as DPYD*2A(rs3918290), DPYD*9(rs1801265), DPYD*5, rs2297595, DPYD*6, rs17376848, rs56038477, DPYD*4(rs1801158), rs67376798 and rs75017182 with Africans (AFR), Amish (AMI), Lati n Americans (AMR), Ashkenazi Jewish (ASJ), East Asians (EAS), Finnish (FIN) and Non-Finnish (NFE). Allele frequencies were obtained from the Genome Aggregati on Database in the PharmGKB database. Χ² analysis was performed. p<0.05 was deemed to be stati sti cally signifi cant. The study found a signifi cant diff erence between the SAS populati on and AFR, AMR, ASJ, EAS, FIN and NFE populati ons for the DPYD*9A gene variant, except for the AMI populati on. The distributi on of the DPYD*2A gene variant of SAS was found to be signifi cant in the AFR, ASJ, FIN and NFE populati ons, except for AMR and AMI. The prevalence of DPYD*5, DPYD*6, rs17376848, and rs56038477 in the SAS signifi cantly diff ered from all above-menti oned populati ons. The distributi on of the rs75017182 gene variant in SAS has shown signifi cant diff erences with AFR, AMR, ASJ and EAS except for NFE and FIN. This study highlights the variati ons in pharmacogenomics data specifi c to populati ons that could lead to personalized medicine and the need for DPYD genotyping before cancer treatment, especially in SAS communiti es where clinically signifi cant geneti c variati ons and haplotypes occur. Study fi ndings pinpoint the potenti al contributi on of DPYD gene variati ons to individual variability in anti -cancer dosage requirements among SAS.
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    PublicationOpen Access
    A Study on the Diversity of Pharmacogenomic Variants Aff ecti ng Dapsone Hypersensiti vity: A Comparati ve Study Based on South Asian and Other World Populati ons
    (Faculty of Humanities and Sciences, SLIIT, 2024-12-04) Weerasinghe, M; Perera, N; Kasthuriarachchi, J; Ranasinghe, P
    Recent data from Sri Lanka indicates an increase in leprosy cases, emphasizing the necessity of dapsone as a drug vital for managing it. Ironically, dapsone eff ecti veness is accompanied by dapsone hypersensiti vity syndrome (DHS) which varies among populati ons. We postulate that this is due to signifi cant diff erences between SNP frequencies in HLA-B*13:01, CYP2C9*3, rs701829, rs17211071, and rs201929247. As per our reading, no comparati ve study has been done so far on DHS and related genes between South Asian (SAS) and other world populati ons. Therefore, this study compares the allele frequencies of SNPs from PharmGKB and dbSNP of world populati ons against SAS using chisquare (χ²) tests. For HLA-B*13:01; it is reported that Europeans, Africans, African others, and African Americans have demonstrated signifi cant diff erences, and Asians, EAS, Other Asians, and Lati n Americans have shown no signifi cant diff erences. For CYP2C9*3 and rs701829; Americans, Africans, Amish, Ashkenazi Jews, East Asians (EAS), Finns, and Non-Finnish Europeans (NFE) all have demonstrated a signifi cant diff erence from SAS. For rs17211071, Africans, Amish, Americans, East Asians, Finns, and NFE demonstrated no signifi cant diff erence, and ASJ showed a signifi cant diff erence. For rs201929247, Africans and Finns had no signifi cant diff erences, whereas Americans, Amish, ASJ, EAS, and NFE had. Hence, compared with other populati ons, allele frequencies of some studied SNPs were signifi cantly diff erent in SAS, and these may likely account for the variability of DHS occurrence among these populati ons. Signifi cant allele frequency diff erences between SAS and the rest of the world populati ons’ impact personalized medicine in leprosy treatment. Clinical research needs to determine the opti mal dapsone dose alterati ons, considering environmental and other factors behind DHS.