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Drug Metabolism and Personalized Therapy

Official journal of the European Society of Pharmacogenomics and Personalised Therapy

Editor-in-Chief: Llerena, Adrián

Editorial Board: Benjeddou, Mongi / Chen, Bing / Dahl, Marja-Liisa / Devinsky, Ferdinand / Hirata, Rosario / Hubacek, Jaroslav A. / Ingelman-Sundberg, Magnus / Maitland-van der Zee, Anke-Hilse / Manolopoulos, Vangelis G. / Marc, Janja / Melichar, Bohuslav / Meyer, Urs A. / Nair, Sujit / Nofziger, Charity / Peiro, Ana / Sadee, Wolfgang / Salazar, Luis A. / Simmaco, Maurizio / Turpeinen, Miia / Schaik, Ron / Shin, Jae-Gook / Visvikis-Siest, Sophie / Zanger, Ulrich M.

4 Issues per year

CiteScore 2017: 1.46

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Volume 33, Issue 1


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

Swarup A.V. ShahORCID iD: http://orcid.org/0000-0003-1703-5990 / Minal U. Paradkar
  • Research Laboratories, P.D. Hinduja National Hospital and Medical Research Centre, V.S. Marg, Mahim, Mumbai, India
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Devendra C. Desai
  • Department of Gastroenterology, P.D. Hinduja National Hospital and Medical Research Centre, V.S. Marg, Mahim, Mumbai, India
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Tester F. Ashavaid
  • Corresponding author
  • Consultant Biochemist, Head – Department of Laboratory Medicine, Director – Lab Research, Department of Biochemistry, P.D. Hinduja National Hospital and Medical Research Centre, Veer Savarkar Marg, Mahim, Mumbai 400-016, India, Phone: +91 022 24447935, Fax: +91 022 24442318, E-mail:
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-02-22 | DOI: https://doi.org/10.1515/dmpt-2017-0038



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 statistically significant difference in thiopurine dose requirement for patients with the NUDT15 variant.


A preemptive NUDT15 genotyping approach can therefore help identify high-risk patients (NUDT15 C415T positive) who could benefit from thiopurine dose reduction, thereby preventing fatal thiopurine-induced toxicity.

Keywords: Indians; NUDT15; preemptive genotyping; thiopurine toxicity; TPMT


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About the article

Received: 2017-11-22

Accepted: 2018-01-23

Published Online: 2018-02-22

Published in Print: 2018-03-28

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: National Health Education Society of P.D. Hinduja National Hospital and Medical Research Centre.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interest: All authors have no conflict of interest to declare. The funding organization played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Drug Metabolism and Personalized Therapy, Volume 33, Issue 1, Pages 57–60, ISSN (Online) 2363-8915, ISSN (Print) 2363-8907, DOI: https://doi.org/10.1515/dmpt-2017-0038.

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