Higher prevalence of NUDT15 rs116855232 compared to TPMT rs1142345 in a Chinese cohort and its implications for thiopurine therapy

Background Thiopurine drugs are widely used as immunosuppressants and chemotherapeutic agents in clinical practice, but their adverse effects significantly limit their clinical application. TPMT c.719A>G (rs1142345) and NUDT15 c.415C>T (rs116855232) are the most common genetic polymorphisms influencing thiopurine drug toxicity, with notable differences in allele frequencies across diverse populations. However, there remains a paucity of research on the NUDT15 c.415C>T polymorphism in the Chinese population. Methods This study enrolled 571 Chinese patients. DNA samples were isolated, and polymerase chain reaction (PCR) was performed to amplify the TPMT c.719A>G and NUDT15 c.415C>T in each sample. PCR products were genotyped via Sanger sequencing to identify the allelic frequencies of these polymorphisms. Additionally, we compared the detection rate of NUDT15 c.415C>T and TPMT c.719A>G for thiopurine drug toxicity in the cohort. Results The minor allele frequencies of NUDT15 c.415C>T and TPMT c.719A>G were determined to be 12.52% and 2.36%, respectively. The detection rate of the NUDT15 c.415C>T polymorphism was significantly higher than that of TPMT c.719A>G (23.47% vs. 4.55%, P < 0.001). Conclusion NUDT15 c.415C>T yielded a higher carrier rate than TPMT c.719A>G in this cohort. And broader panels could shift absolute yields. These findings highlight the critical role of NUDT15 c.415C>T genotyping in guiding precision therapy with thiopurine drugs.