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

Abstract

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.