In Silico Analysis of the Diversity of DPYD Gene Variants Affecting Fluoropyrimidine Toxicity: A Comparison of South Asians with Other World Populations

Fluoropyrimidine (FP) chemotherapy drug is utilized to treat colon, head, neck and breast cancers. Apart from its effectiveness, toxicity is a limitation. DPD (dihydropyrimidine dehydrogenase) enzyme, which aids in the FP metabolism is produced by the highly polymorphic DPYD gene. Mutations in the DPYD gene cause the deficiency or non-functionality of the DPD enzyme which varies among different populations. 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 Aggregation Database in the PharmGKB database. Χ² analysis was performed. p<0.05 was deemed to be statistically significant. The study found a significant difference between the SAS population and AFR, AMR, ASJ, EAS, FIN and NFE populations for the DPYD*9A gene variant, except for the AMI population. The distribution of the DPYD*2A gene variant of SAS was found to be significant in the AFR, ASJ, FIN and NFE populations, except for AMR and AMI. The prevalence of DPYD*5, DPYD*6, rs17376848, and rs56038477 in the SAS significantly differed from all above-mentioned populations. The distribution of the rs75017182 gene variant in SAS has shown significant differences with AFR, AMR, ASJ and EAS except for NFE and FIN. This study highlights the variations in pharmacogenomics data specific to populations that could lead to personalized medicine and the need for DPYD genotyping before cancer treatment, especially in SAS communities where clinically significant genetic variations and haplotypes occur. Study findings pinpoint the potential contribution of DPYD gene variations to individual variability in anti -cancer dosage requirements among SAS. Keywords: Pharmacogenomics; Personalized medicine; Fluoropyrimidine; Fluoropyrimidine toxicity; South Asians