Identification of NUDT15*3 Variant in the Bangladeshi Population using Allele-Specific PCR

Background: Thiopurines are a class of immunosuppressive drugs that are often the mainstay of treatment for diverse immunological and malignant conditions. The protein product of the gene NUDT15 (nudix hydrolase 15) has been linked to thiopurine metabolism as it negatively regulates thiopurine activation and toxicity. A missense variant of the gene, NUDT15*3 (rs116855232, c.415C>T, and p.R139C), has been the most reported NUDT15 single nucleotide polymorphism in the literature. Objective: In this study, we devised an allele-specific polymerase chain reaction (ASPCR) assay to determine genotype at the rs116855232 locus and employed the method to estimate allele frequencies in the Bangladeshi population. Materials and methods: A total of 184 randomly selected individuals were recruited in this study. The allele frequencies of the NUDT15*3 variant (rs116855232) in the Bangladeshi population and genotypes at the locus were determined by ASPCR. The ASPCR genotype data were validated by Sanger sequencing to ascertain the reliability of the assay. Results: NUDT15 *1/*1 and NUDT15 *1/*3 genotype frequencies were 83.70% and 16.70%, respectively, while no instances of NUDT15 *3/*3 genotype were observed. Estimated allele frequencies of C and T alleles were 0.924 and 0.076, respectively. Conclusion: Overall, this study provides a comprehensive account of the distribution of the debilitating SNP and proposes a time- and cost-efficient pharmacogenetic testing procedure that may inform personalized thiopurine therapy.