Preemptive NUDT15 genotyping: redefining the management of patients with thiopurine-induced toxicity.

Drug Metabolism and Personalized Therapy
Swarup A V ShahTester F Ashavaid

Abstract

Thiopurine methyltransferase (TPMT) gene variants have achieved limited success in predicting the outcome of thiopurine therapy, which shows wide inter-individual variations. The literature indicates a strong association between the NUDT15 gene variant and thiopurine-induced toxicity in Asian patients. The present study intends to explore the role of the NUDT15 variant (C415T) in Indian patients on thiopurine therapy. NUDT15 and TPMT genotyping were performed using amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) and the restriction fragment length polymorphism (RFLP) technique. Of 370 samples received for TPMT testing, 206 samples were available for NUDT15 genotyping. The NUDT15 risk allele frequency was 10.7%, with the frequency of wild, heterozygous and mutant genotypes being 80.6%, 17.5% and 1.9%, respectively. TPMT variants were seen in 13 of 370 (3.5%) patients, whereas the NUDT15 variant was seen in 40 of 206 (19.4%) patients. Thiopurine-induced toxicity information was available for 101 patients, among whom 10 developed leukopenia and all harbored the NUDT15 variant (p<0.0001). NUDT15 was clinically more relevant than TPMT in terms of sensitivity and specificity, as well as with a statistica...Continue Reading

References

Jan 29, 2011·Clinical Pharmacology and Therapeutics·M V RellingUNKNOWN Clinical Pharmacogenetics Implementation Consortium
Jan 28, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jun J YangMary V Relling
Feb 16, 2016·Nature Genetics·Takaya MoriyamaJun J Yang
Jul 16, 2016·Journal of Gastroenterology and Hepatology·Swarup A V ShahTester F Ashavaid

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Citations

Aug 18, 2020·European Journal of Clinical Pharmacology·Mihika B DaveTester F Ashavaid
Sep 17, 2020·Pharmacological Reports : PR·Shaik Mohammad NaushadSalman A Alrokayan
Mar 13, 2021·Indian Journal of Critical Care Medicine : Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine·Prasanta DebnathPravin Rathi

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Methods Mentioned

BETA
genotyping

Software Mentioned

MEDCALC
GRAPHPAD PRISM

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