A Study on the Diversity of Pharmacogenomic Variants Affecting Dapsone Hypersensitivity: A Comparative Study Based on South Asian and Other World Populations

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 effectiveness is accompanied by dapsone hypersensitivity syndrome (DHS) which varies among populations. We postulate that this is due to significant differences between SNP frequencies in HLA-B*13:01, CYP2C9*3, rs701829, rs17211071, and rs201929247. As per our reading, no comparative study has been done so far on DHS and related genes between South Asian (SAS) and other world populations. Therefore, this study compares the allele frequencies of SNPs from PharmGKB and dbSNP of world populations against SAS using chi- square (χ²) tests. For HLA-B*13:01; it is reported that Europeans, Africans, African others, and African Americans have demonstrated significant differences, and Asians, EAS, Other Asians, and Latin Americans have shown no significant differences. For CYP2C9*3 and rs701829; Americans, Africans, Amish, Ashkenazi Jews, East Asians (EAS), Finns, and Non-Finnish Europeans (NFE) all have demonstrated a significant difference from SAS. For rs17211071, Africans, Amish, Americans, East Asians, Finns, and NFE demonstrated no significant difference, and ASJ showed a significant difference. For rs201929247, Africans and Finns had no significant differences, whereas Americans, Amish, ASJ, EAS, and NFE had. Hence, compared with other populations, allele frequencies of some studied SNPs were significantly different in SAS, and these may likely account for the variability of DHS occurrence among these populations. Significant allele frequency differences between SAS and the rest of the world populations’ impact personalized medicine in leprosy treatment. Clinical research needs to determine the optimal dapsone dose alterations, considering environmental and other factors behind DHS. Keywords: Pharmacogenomics; Personalized Medicine; Leprosy; DHS; Dapsone