Nucleoside diphosphate-linked moiety X-type motif 15 C415T variant as a predictor for thiopurine-induced toxicity in Indian patients

Interindividual variation seen in the thiopurine metabolism is attributed to the genetic variant in thiopurine methyltransferase (TPMT) gene leading to myelosuppression. In Asians, the thiopurine-induced toxicity is not completely explained by TPMT variants. Literature indicates that a newer genetic variant in nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) gene is associated with thiopurine intolerance. We aimed to determine the risk allele frequency of NUDT15 genetic variant and its association with thiopurine-induced toxicity in Indian patients. In this pilot study, 69 patients on thiopurine therapy were analyzed. The frequencies of thiopurine-induced leukopenia were recorded. NUDT15 (C415T) and TPMT (*2, *3A, *3B, and *3C) genotyping was performed using amplification refractory mutation system-polymerase chain reaction and restriction fragment length polymorphism technique. Results were validated by DNA sequencing. The NUDT15 CC, CT, and TT genotypes were found to be 86.9%, 11.5%, and 1.5%, respectively, whereas TPMT genetic variants were absent. Of 60 patients without NUDT15 variant, none developed leukopenia, whereas of nine patients with NUDT15 variant, six developed leukopenia (P-value